CA3143994A1 - Compositions and methods of treating a th2-mediated condition using prevotella - Google Patents

Abstract

Provided herein are compositions and methods related to Prevotella bacteria that can be useful as therapeutic agents, for example for the treatment of a TH2-mediated condition, such as atopic dermatitis, and/or a food allergy.

Description

CONDITION USING PREVOTELLA
RELATED APPLICATIONS
[1] This application claims a right of priority to and the benefit of the filing date of U.S. Provisional Application No. 62/864,886, filed on June 21, 2019, and U.S.
Provisional Application No. 62/910,920, filed on October 4, 2019, both of which are hereby incorporated by reference in their entirety.
BACKGROUND

[2] Helper T (TH) cells (also referred to as CD4+ T cells) coordinate adaptive immune responses through the secretion of cytokines that influence the activities of other immune cells, including B cells, other T cells, eosinophils, basophils, mast cells, and macrophages.

[3] When a naive TH cell becomes activated it differentiates into one of various TH
cell subsets, each of which is responsible for coordinating an aspect of the immune response through the secretion of a certain set of cytokines. For example, TH1 cells secrete IFN-y and are responsible for enhancing cell-mediated immune responses against viruses and intracellular bacteria. TH2 cells, on the other hand, secrete IL-4, IL-5, IL-9, IL-10, IL-13, and IL-25 and are responsible, inter alia, for enhancing a humoral immune response against extracellular parasites, such as helminths. TH17 cells secrete IL-17 and mediate inflammatory responses, such as responses against fungi (among other pathogens).

[4] The TH subset into which a TH cell differentiates upon activation is determined, in part, by the presence of certain polarizing cytokines. For example, if a naive TH cell is activated in the presence of IFN-y, it will likely differentiate into a TH1 cell. On the other hand, if a naive TH cell is activated in the presence of IL-4, it will likely differentiate into a TH2 cell. Thus, secretion of IFN-y by activated TH1 cells can lead to other TH cells to polarize to the TH1 subset, whereas secretion of IL-4 by activated TH2 cells can lead to other TH cells to polarize to the TH2 subset. Because of this cascading effect, TH cell differentiation can have widespread effects to a person's global immune response. Indeed, a number of diseases and disorders have been associated with TH2 immune responses, including (but not limited to) allergies (e.g., food allergies, insect-induced allergies, drug allergies, or allergic rhinitis), asthma, and atopic dermatitis.

[5] Thus, there is a need for new compositions and methods for promoting a immune response and/or inhibiting a TH2 immune response in order to treat such TH2-mediated conditions.
SUMMARY

[6] As disclosed herein, pharmaceutical compositions including bacteria of the genus Prevotella have therapeutic effects and are useful for the treatment and/or prevention (i.e., for treatment, for prevention, or for both treatment and prevention) of one or more TH2-mediated conditions. Such TH2-mediated conditions include, but are not limited to, allergic rhinitis, asthma, atopic dermatitis, urticaria, angioedema, allergy (such as food allergy, insect-induced allergy, drug allergy), anaphylaxis, and eosinophilia.

[7] In some aspects, provided herein are methods for treating and/or preventing a TH2-mediated condition of a subject. In certain embodiments, the methods include administering to the subject a therapeutically effective amount of a pharmaceutical composition that includes bacteria of the genus Prevotella.

[8] In certain aspects, provided herein are pharmaceutical compositions including bacteria of the genus Prevotella that are useful for the treatment or prevention of one or more TH2-mediated conditions. Thus, in certain aspects, provided herein are pharmaceutical compositions including bacteria of the genus Prevotella for use in the treatment or prevention of a TH2-mediated condition.

[9] In certain aspects, provided herein are uses of a pharmaceutical composition including bacteria of the genus Prevotella for the preparation of a medicament for the treatment or prevention of a TH2-mediated condition.

[10] In certain embodiments, the TH2-mediated condition is an allergy, atopic dermatitis, asthma, urticaria, angioedema, anaphylaxis, eosinophilia, or a combination thereof.

[11] In some embodiments TH2-mediated condition is an allergy. In certain embodiments, the allergy is allergic rhinitis, a food allergy, an insect-induced allergy, or a drug allergy. In some embodiments, the allergy is a food allergy. In some embodiments, the food allergy can include an allergy to eggs, milk, peanuts, tree nuts (e.g., walnuts), fish, shellfish, wheat, soy, or a combination thereof.

[12] In some embodiments of any one of these aspects, the subject is a human. In some embodiments, the subject is a non-human animal.

[13] In some embodiments, at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of the total microbial content of the pharmaceutical composition is bacteria of the genus Prevotella or is biological material derived from bacteria of the genus Prevotella.

[14] In certain embodiments of any one of the aspects disclosed herein, the bacteria of the genus Prevotella includes at least one protein having an amino acid sequence selected from SEQ ID NOs: 1 to 41. Additionally, or separately, in some embodiments, the bacteria of the genus Prevotella are substantially free of at least one or more of each protein having an amino acid sequence selected from SEQ ID NOs: 42 to 69.

[15] In some embodiments of any one of the aspects disclosed herein, the bacteria of the genus Prevotella include bacteria of the species Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccahs, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella orahs, Prevotella oris, Prevotella oulorum, Prevotella pa/lens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella den tasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella muhisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, Prevotella verorahs, or a combination thereof. In some embodiments, the bacteria of the genus Prevotella can include bacteria of the species Prevotella histicola.

[16] In some embodiments, the bacteria of the genus Prevotella can includes a strain that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% (e.g., at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100%) genomic, 16S ribosomal ribonucleic acid, and/or clustered regularly interspaced short palindromic repeats sequence identity with Prevotella histicola strain B 50329 (NRRL accession: B 50329). In some embodiments, the bacteria of the genus Prevotella include Prevotella histicola strain B 50329 (NRRL accession: B 50329).

[17] In some embodiments, the Prevotella bacteria is a strain of Prevotella bacteria comprising a protein listed in Table 1 and/or a gene encoding a protein listed in Table 1. In some embodiments, the Prevotella bacteria is a strain of Prevotella bacteria free or substantially free of a protein listed in Table 2 and/or a gene encoding a protein listed in Table 2. In some embodiments, the Prevotella histicola bacteria is a strain of Prevotella histicola bacteria comprising a protein listed in Table 1 and/or a gene encoding a protein listed in Table 1. In some embodiments, the Prevotella histicola bacteria is a strain of Prevotella histicola bacteria free or substantially free of a protein listed in Table 2 and/or a gene encoding a protein listed in Table 2.

[18] In certain embodiments, the pharmaceutical composition comprises a single species of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises a plurality of species of Prevotella bacteria (e.g., 2, 3, 4, 5 species). In certain embodiments, the pharmaceutical composition comprises a single strain of Prevotella bacteria.
In some embodiments, the pharmaceutical composition comprises a plurality of strains of Prevotella bacteria (e.g., 2, 3, 4, 5 strains). In certain embodiments, the pharmaceutical composition comprises a single strain of Prevotella histicola bacteria. In some embodiments, the pharmaceutical composition comprises a plurality of strains of Prevotella histicola bacteria (e.g., 2, 3, 4, 5 strains).

[19] In some embodiments, the bacteria of the genus Prevotella of the pharmaceutical composition include live, killed, or attenuated bacteria. In some embodiments, the bacteria of the genus Prevotella of the pharmaceutical composition include live bacteria. In some embodiments, the pharmaceutical composition includes gamma-irradiated, UV irradiated, heat inactivated (e.g., at 50 C for two hours, at 90 C for two hours), acid treated, or oxygen sparged (e.g., at 0.1 vvm for two hours) bacteria. In certain embodiments, the bacteria of the genus Prevotella of the pharmaceutical composition includes lyophilized bacteria. In some embodiments, the pharmaceutical composition further includes a pharmaceutically acceptable excipient.

[20] In some embodiments of any one of the aspects disclosed herein, the administration of the pharmaceutical composition to a subject can cause decrease in the level of a TH2-protein and/or an mRNA encoding a TH2-protein in the subject (e.g., in a mesenteric lymph node or cervical lymph node thereof). For instance, in certain embodiments, upon administration of the pharmaceutical composition, the level of the TH2-protein and/or an mRNA
encoding a TH2-protein becomes lower in the subject as compared the level of the TH2-protein and/or an mRNA encoding a TH2-protein before the administration of the pharmaceutical composition. In certain embodiments, the TH2-protein is interleukin-4 (IL-4), interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-31, interleukin-33, thymic stromal lymphopoietin, immunoglobulin Gl, immunoglobulin E, immunoglobulin A, or a combination thereof. In certain embodiments, the TH2-protein is IL-4, IL-13, IL-5, IL-31, IL-33 or a combination thereof. In certain embodiments, the TH2-protein is IL-13, IL-5, IL-31 or a combination thereof. In certain embodiments, the TH2-protein is IL-13. In certain embodiments, the TH2-protein is IL-31. In certain embodiments, the TH2-mRNA is 114, 115, IL 31, 1133, Tslp, Cc19, Ccr4 or a combination thereof. In certain embodiments, the TH2-mRNA is 114, 115, 1133, 1117a, Il lb, Tslp or a combination thereof. In certain embodiments, the TH2-mRNA is 114, 115, Tslp, Ccr4, 1119 or a combination thereof. In certain embodiments, the TH2-mRNA is 115, 1131, and Ccr4 or a combination thereof. In certain embodiments, the TH2-mRNA is 115.

[21] In some embodiments of any one of the aspects disclosed herein, the administration of the pharmaceutical composition to a subject can cause a decrease in the level of a mast cell related protein and/or an mRNA encoding a mast cell related protein in the subject (e.g., in the jejunum thereof). In certain embodiments, the mast cell mRNA is Mcptl . For instance, in certain embodiments, upon administration of the pharmaceutical composition, the level of the mast cell related protein and/or an mRNA encoding the mast cell related protein becomes lower in the subject as compared the level of the mast cell related protein and/or an mRNA encoding the mast cell related protein before the administration of the pharmaceutical composition.

[22] In some embodiments of any one of the aspects disclosed herein, the administration of the pharmaceutical composition to a subject can cause an increase in the level of IL-10 in the subject (e.g., in the spleen or a mesenteric lymph node thereof). For instance, in certain embodiments, upon administration of the pharmaceutical composition, the level of IL-10 and/or mRNA encoding IL-10 becomes higher in the subject (e.g., in the spleen or a mesenteric lymph node thereof) as compared the level of IL-10 and/or mRNA encoding IL-10 before the administration of the pharmaceutical composition.

[23] In some embodiments of any one of the aspects disclosed herein, an additional therapeutic agent is administered to the subject. In some embodiments, the additional agent is an anti-inflammatory agent. In certain embodiments the additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukatriene receptor antagonist, an antibody, or a combination thereof For example, the additional therapeutic agent can be acrivastine, albuterol, alimemazine, ANB020, andbenralizumab, antazoline, AS1517499, AS1810722, astemizole, azathioprine, AZD1981, azelastine, beclomethasone, bepotastine, betamethasone, BI671800, bilastine, bromazine, brompheniramine, budesonide, budesonide-formoterol, carbinoxamine, cetirizine, chlorcyclizine, chloropyramine, chlorphenamine, ciclesonide, ciclosporin, cimetidine, clemastine, cortisone, crisaborole., cromolyn, cyclizine, cyproheptadine, CYT003., dapsone, desloratadine, dexamethasone, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, dupilumab, ebastine, ephedrine, epinephrine, famotidine, fexofenadine, flunisolide, fluticasone, fluticasone furoate, fluticasone propionate, fluticasone-salmeterol, formoterol, formoterol-mometasone, GSK3772847, hydroxychloroquine, hydroxyzine, imiquimod, interferongamma-lb, ipratropium, ketotifen, lebrikizumab, levalbuterol, levocabastine, levocetirizine, levomethamphetamine, loratadine, meclizine, meclofenamate sodium, mepolizumab, mepyramine, methotrexate, methylprednisolone, mizolastine, MK-886, mometasone, montelukast, mycophenolate, mycophenolatemofetil, naphazoline, 00000459, olopatadine, omalizumab, orphenadrine, oxymetazoline, pheniramine, phenylephrine, phenylpropanolamine, pimecrolimus, prednisolone, prednisone, promethazine, propylhexedrine, pseudoephedrine, quifenadine, ranitidine, resiquimod, resulizumab, RG6149/AMG282, rupatadine, salmeterol, SB010, sirolimus, sulfasalazine, synephrine, tacrolimus, terfenadine, tetryzoline, theophylline, tixocortol, tralokinumab, tramazoline, triamcinolone, triamcinolone acetonide, tripelennamine, triprolidine, vitaminD, xylometazoline, YM-341619, zafirlukast, zileuton, or a combination thereof. In certain embodiments, the additional therapeutic agent can be included as a part of the pharmaceutical composition or it can be separate.

[24] In some embodiments, the pharmaceutical composition is administered by oral, intravenous, subcutaneous, intradermal, or intraperitoneal administration. In some embodiments, the pharmaceutical composition is administered by oral administration.

[25] In certain embodiments, the pharmaceutical composition can include a total protein amount of at least 5 mg (e.g., at least 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg, 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 660 mg, 670 mg, 680 mg, 690 mg, 700 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, or 900 mg,) and no more than 900 mg (e.g., no more than 890 mg, 880 mg, 870 mg, 860 mg, 850 mg, 840 mg, 830 mg, 820 mg, 810 mg, 800 mg, 790 mg, 780 mg, 770 mg, 760 mg, 750 mg, 740 mg, 730 mg, 720 mg, 710 mg, 700 mg, 690 mg, 680 mg, 670 mg, 660 mg, 650 mg, 640 mg, 630 mg, 620 mg, 610 mg, 600 mg, 590 mg, 580 mg, 570 mg, 560 mg, 550 mg, 540 mg, 530 mg, 520 mg, 510 mg, 500 mg, 490 mg, 480 mg, 470 mg, 460 mg, 450 mg, 440 mg, 430 mg, 420 mg, 410 mg, 400 mg, 390 mg, 380 mg, 370 mg, 360 mg, 350 mg, 340 mg, 330 mg, 320 mg, 310 mg, 300 mg, 290 mg, 280 mg, 270 mg, 260 mg, 250 mg, 240 mg, 230 mg, 220 mg, 210 mg, 200 mg, 190 mg, 180 mg, 170 mg, 160 mg, 150 mg, 140 mg, 130 mg, 120 mg, 110 mg, 100 mg, 90 mg, 80 mg, 70 mg, 60 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg) (e.g., as determined by a Bradford assay, as determined by a BCA
assay). In certain embodiments, the pharmaceutical composition can include a total protein amount of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, or about 900 mg (e.g., as determined by a Bradford assay, or as determined by a BCA assay).

[26] In some embodiments, the pharmaceutical composition can include a total amount of bacteria of the genus Prevotella of at least 5 mg (e.g., at least 6 mg, at least 7 mg, at least 8 mg, at least 9 mg, at least 10 mg, at least 11 mg, at least 12 mg, at least 13 mg, at least 14 mg, at least 15 mg, at least 16 mg, at least 17 mg, at least 18 mg, at least 19 mg, or at least 20 mg) and no more than 20 mg (e.g., no more than 19 mg, no more than 18 mg, no more than 17 mg, no more than 16 mg, no more than 15 mg, no more than 14 mg, no more than 13 mg, no more than 12 mg, no more than 11 mg, no more than 10 mg, no more than 9 mg, no more than 8 mg, no more than 7 mg, no more than 6 mg, no more than 5 mg) (e.g., as determined by a Bradford assay, or as determined by a BCA assay). In some embodiments, the pharmaceutical composition can include a total amount of bacteria of the genus Prevotella of about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, or about 20 mg (e.g., as determined by a Bradford assay, or as determined by a BCA assay).

[27] In certain embodiments, the pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises at least 1 x 1010 total cells (e.g., at least 1 x 1010 total cells, at least 2 x 1010 total cells, at least 3 x 1010 total cells, at least 4 x 1010 total cells, at least 5 x 1010 total cells, at least 6 x 1010 total cells, at least 7 x 1010 total cells, at least 8 x 1010 total cells, at least 9 x 1010 total cells, at least 1 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises no more than 9 x 1011 total cells (e.g., no more than 1 x 1010 total cells, no more than 2 x 1010 total cells, no more than 3 x 1010 total cells, no more than 4 x 1010 total cells, no more than 5 x 1010 total cells, no more than 6 x 1010 total cells, no more than 7 x 1010 total cells, no more than 8 x 1010 total cells, no more than 9 x 1010 total cells, no more than 1 x 1011 total cells, no more than 2 x 1011 total cells, no more than 3 x 1011 total cells, no more than 4 x 1011 total cells, no more than 5 x 1011 total cells, no more than 6 x 1011 total cells, no more than 7 x 1011 total cells, no more than 8 x 1011 total cells) of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 6 x 109 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 101 total cells of the Prevotella bacteria.
In some embodiments, the pharmaceutical composition comprises about 8 x 1010 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1011 total cells the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 3.2 x 1011 total cells the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1010 to about 8 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1010 to about 1.6 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8 x 1010 to about 8 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1011 to about 8 x 1011 total cells of the Prevotella bacteria.

[28] In certain embodiments, provided herein are solid dosage forms comprising the Prevotella bacteria. In some embodiments, the solid dosage form comprises an enteric coating.
In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 8 x 1010 total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 8 x 1010 total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 8 x 1010 total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 8 x 1010 total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 8 x 1010 total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder).

[29] In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated tablet. In some embodiments, the capsule comprises about 8 x 1010 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 1.6 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 3.2 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 8 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder).

[30] In some embodiments, the solid dosage form comprises a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 17mm in diameter. In some embodiments, the tablet comprises about 8 x 1010 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 1.6 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 3.2 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 8 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[31] In some embodiments, the solid dosage form comprises a mini-tablet. In some embodiments, the mini-tablet is enteric coated. In some embodiments, the mini-tablet is from 1 mm to 4mm in diameter. In some embodiments, the mini-tablet (e.g., enteric coated mini-tablet) is a 1 mm 1.5 mm mini-tablet, 2mm mini-tablet, 3mm mini-tablet, or 4mm mini-tablet. In some embodiments, the solid dosage form comprises mini-tablets that comprise about 8 x 1010 total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets that comprise about 1.6 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets that comprise about 3.2 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets that comprise about 8 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the Prevotella bacteria in the mini-tablets are lyophilized.

[32] In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) are contained in a capsule. In some embodiments, the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule comprises a non-enteric coating (e.g., HPMC (hydroxyl propyl methyl cellulose) or gelatin) (e.g., is coated with a non-enteric coating). In some embodiments, the capsule comprises a non-enteric coating. In some embodiments, the capsule comprises hydroxyl propyl methyl cellulose (HPMC). In some embodiments, the capsule comprises gelatin. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) that comprise about 8 x 10" total cells of the Prevotella bacteria are contained in a capsule(s), wherein optionally the capsule comprises HPMC.

[33] In some embodiments, the pharmaceutical composition comprising Prevotella bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a minitablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., minitablets comprised in a capsule). In certain embodiments, the powder can comprise lyophilized bacteria.

[34] In certain embodiments of any one of the aspects disclosed herein, the pharmaceutical composition is formulated as a solid dose form. In some embodiments, the pharmaceutical composition has a dose form selected from a tablet, a capsule, a minitablet, a powder, or a combination thereof. In some embodiments, the pharmaceutical composition is formulated as a suspension (e.g., in PBS). In some embodiments, pharmaceutical composition formulated for oral, intravenous, subcutaneous, intradermal, and/or intraperitoneal administration. In some embodiments, pharmaceutical composition is formulated for oral administration.

[35] In some embodiments, the pharmaceutical composition comprises lyophilized Prevotella bacteria. In certain embodiments, the lyophilized Prevotella bacteria is formulated into a solid dose form, such as a tablet, a minitablet, a capsule, a pill, or a powder. In some embodiments, the lyophilized Prevotella bacteria is contained in a capsule. In some embodiments, the lyophilized Prevotella bacteria is resuspended in a solution.

[36] In certain embodiments, provided herein are methods of treating a subject who has a TH2-mediated condition, the method comprising administering to the subject a pharmaceutical composition described herein.

[37] In certain embodiments, provided herein are methods of treating a subject who has atopic dermatitis, the method comprising administering to the subject a pharmaceutical composition described herein.

[38] In certain embodiments, provided herein are methods of treating a subject who has a food allergy, the method comprising administering to the subject a pharmaceutical composition described herein.

[39] In some embodiments, the methods provided herein further comprise administering to the subject an antibiotic. In some embodiments, the methods further comprise administering to the subject one or more other therapies for the condition. In some embodiments, the methods further comprise the administration of another therapeutic bacterium.
BRIEF DESCRIPTION OF THE FIGURES

[40] Figure 1A is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling at 8h post FITC ear challenge in a FITC-driven contact hypersensitivity model. (Ordinary one-way ANOVA; p<0.001 for dexamethasone; p:
0.0031 for P. histicola.)

[41] Figure 1B is a series of graphs showing that Prevotella histicola treatment reduced gene expression for 114, 115, 1133, 1117a, Il lb, and Tslp in the ears.

[42] Figure 2 is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling at 8h post FITC ear challenge in a FITC-driven contact hypersensitivity model. (Ordinary one-way ANOVA; Strain 1 is a strain of another species of Prevotella; and Strain 2 is a strain of a different genus than Prevotella.)

[43] Figure 3A shows a study design for a model of atopic dermatitis-associated food allergy.

[44] Figure 3B is a graph showing that oral administration of Prevotella histicola significantly reduced ear inflammation in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen model. (Ordinary one-way ANOVA; p: 0.0009 for tofacitinib; p <0.0001 for P. histicola; p: 0.0047 for Strain B; Strain A is a strain of a different genus than Prevotella; and Stain B is another strain of Prevotella histicola.)

[45] Figure 3C is a pair of graphs showing IgG1 and IgE levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen (Strain A is a strain of a different genus than Prevotella; and Stain B is another strain of Prevotella histicola.).

[46] Figure 3D is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31 and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin(OVA) food allergen (Strain A is a strain of a different genus than Prevotella; and Stain B is another strain of Prevotella histicola.).

[47] Figure 4A shows a study design for a mouse model testing an atopic dermatitis-associated food allergy model using ovalbumin (OVA) or CPE (complete peanut extract) as food allergen.

[48] Figure 4B is a graph showing that oral administration of Prevotella histicola significantly reduced ear inflammation in both an OVA-driven and a peanut allergen (CPE)-driven atopic dermatitis-associated food allergy model. (Ordinary one-way ANOVA; p: <0.0001 for tofacitinib; p: 0.0024 for anti-IL-4; p: 0.0163 for Strain A; p<0.0001 for P. histicola (OVA
group); p: <0.0001 for CPE group (vehicle versus P. histicola); Strain A is a strain of a different genus than Prevotella.)

[49] Figure 4C is a pair of graphs showing anti-OVA IgG1 and anti-OVA IgE
levels in mice administered vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("Strain A") in an atopic dermatitis-associated food allergy model using ovalbumin(OVA) food allergen (Strain A is a strain of a different genus than Prevotella).

[50] Figure 4D is a series of graphs showing IL-4, IL-5, IL-13, IL-10 and IL-31 levels in mice administered vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("Strain A") in an atopic dermatitis-associated food allergy model using ovalbumin(OVA) food allergen and vehicle and Prevotella histicola in a peanut allergen (CPE)-driven contact hypersensitivity model (Strain A is a strain of a different genus than Prevotella).

[51] Figure 4E is a series of graphs showing ear IL-4, IL-5, TSLP, CCR4 and RNA levels in mice administered vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("Strain A") in an atopic dermatitis-associated food allergy model using ovalbumin(OVA) food allergen and vehicle and Prevotella histicola in an atopic dermatitis-associated food allergy model using peanut allergen (CPE) as the food allergen (Strain A is a strain of a different genus than Prevotella).

[52] Figure 5 shows an MC903 model of type 2 skin inflammation and food allergy induction.

[53] Figure 6A shows a study design for a cutaneous sensitization peanut allergy model.

[54] Figure 6B shows a study design for a cutaneous sensitization peanut allergy model.

[55] Figure 6C shows a study design for a cutaneous sensitization peanut allergy model.

[56] Figure 6D is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling in a cutaneous sensitization peanut allergy model.

[57] Figure 6E is a pair of graphs showing total IgE and anti-peanut IgE
levels on the day of challenge in mice administered vehicle, tofacitinib ("tofa"), or Prevotella histicola in a cutaneous sensitization peanut allergy model.

[58] Figure 6F is a pair of graphs showing total IgG1 and anti-peanut IgG1 levels on the day of challenge in mice administered vehicle, tofacitinib ("tofa"), or Prevotella histicola in a cutaneous sensitization peanut allergy model.

[59] Figure 6G is a pair of graphs showing total IgE and anti-peanut IgE
levels 2 weeks post-challenge in mice administered vehicle, tofacitinib ("tofa"), or Prevotella histicola in a cutaneous sensitization peanut allergy model.

[60] Figure 6H is a pair of graphs showing total IgG1 and anti-peanut IgG1 levels 2 weeks post-challenge in mice administered vehicle, tofacitinib ("tofa"), or Prevotella histicola in a cutaneous sensitization peanut allergy model.

[61] Figure 61 is a pair of graphs showing total IgA and anti-peanut IgGA
levels 2 weeks post-challenge in mice administered vehicle, tofacitinib ("tofa"), or Prevotella histicola in a cutaneous sensitization peanut allergy model.

[62] Figure 7A is a schematic showing a FITC-CHS model experimental design.

[63] Figure 7B is a series of graphs showing IL-13, IL-4, IL-5, IL-31, and IL-33 levels in ex vivo re-stimulated mesenteric lymph node (mLN) cells from mice that were administered vehicle, dexamethasone or Prevotella histicola in the FITC-CHS model.

[64] Figure 7C is a series of graphs showing IL-13, IL-4, IL-5, IL-31, and IL-33 levels in ex vivo re-stimulated ear draining cervical lymph node (cLN) cells from mice that were administered vehicle, dexamethasone or Prevotella histicola in the FITC-CHS
model.

[65] Figure 8A is a schematic showing the MC903 driven atopic dermatitis model experimental design.

[66] Figure 8B is a pair of graphs showing ear measurements over time (left panel) and ear inflammation on day 14 (right panel) in mice treated with vehicle, tofacitinib, or Prevotella histicola in the MC903 driven atopic dermatitis model.

[67] Figure 8C is a series of graphs showing Tslp, 115, 1131, 114, Cc119, and Ccr4 transcript levels in the ear tissue from mice treated with vehicle, tofacitinib, or Prevotella histicola in the MC903 driven atopic dermatitis model.

[68] Figure 8D is a graph showing mast cell related gene (Mcpt 1) transcript levels in the jejunum from mice treated with vehicle, tofacitinib, or Prevotella histicola in the MC903 driven atopic dermatitis model.

[69] Figure 8E is a pair of graphs showing IL-10 levels in mesenteric lymph nodes (left panel) and spleen (right panel) in mice treated with vehicle, tofacitinib, or Prevotella histicola in the MC903-driven atopic dermatitis model.
DETAILED DESCRIPTION

[70] As disclosed herein, pharmaceutical compositions including bacteria of the genus Prevotella have therapeutic effects and are useful for the treatment or prevention (i.e., for treatment, for prevention, or for both treatment and prevention) of one or more TH2-mediated conditions. Such TH2-mediated conditions include, but are not limited to, allergic rhinitis, asthma, atopic dermatitis, urticaria, angioedema, allergy (e.g. food allergy, insect-induced allergy, or drug allergy), anaphylaxis, and eosinophilia. The pharmaceutical compositions can include Prevotella histicola bacteria.
Definitions

[71] "Adjuvant" or "Adjuvant therapy" broadly refers to an agent that affects an immunological or physiological response in a subject (e.g., human). For example, an adjuvant might increase the presence of an antigen over time or to an area of interest, help absorb an antigen presenting cell antigen, activate macrophages and lymphocytes and support the production of cytokines. By changing an immune response, an adjuvant might permit a smaller dose of an immune interacting agent to increase the effectiveness or safety of a particular dose of the immune interacting agent. For example, an adjuvant might prevent T cell exhaustion and thus increase the effectiveness or safety of a particular immune interacting agent.

[72] "Administration" broadly refers to a route of administration of a composition (e.g., a pharmaceutical composition) to a subject. Examples of routes of administration include oral administration, rectal administration, topical administration, inhalation (nasal) or injection.
Administration by injection includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. A pharmaceutical composition described herein can be administered in any form by any effective route, including but not limited to oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), intradermal, ophthalmic, (intra)nasally, local, non-oral, such as aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, (trans)rectal, vaginal, intra-arterial, and intrathecal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), implanted, intravesical, intrapulmonary, intraduodenal, intragastrical, and intrabronchial. In preferred embodiments, a pharmaceutical composition described herein is administered orally, rectally, topically, intravesically, by injection into or adjacent to a draining lymph node, intravenously, by inhalation or aerosol, or subcutaneously. In another preferred embodiment, a pharmaceutical composition described herein is administered orally or intravenously.

[73] As used herein, the term "antibody" may refer to both an intact antibody and an antigen binding fragment thereof. Intact antibodies are glycoproteins that include at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds.
Each heavy chain includes a heavy chain variable region (abbreviated herein as Vii) and a heavy chain constant region. Each light chain includes a light chain variable region (abbreviated herein as VL) and a light chain constant region. The Vu and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each Vu and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order:
FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The term "antibody"
includes, for example, monoclonal antibodies, polyclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, multispecific antibodies (e.g., bispecific antibodies), single-chain antibodies and antigen-binding antibody fragments.

[74] The terms "antigen binding fragment" and "antigen-binding portion" of an antibody, as used herein, refer to one or more fragments of an antibody that retain the ability to bind to an antigen. Examples of binding fragments encompassed within the term "antigen-binding fragment" of an antibody include Fab, Fab', F(ab')2, Fv, scFv, disulfide linked Fv, Fd, diabodies, single-chain antibodies, NANOBODIES , isolated CDRH3, and other antibody fragments that retain at least a portion of the variable region of an intact antibody. These antibody fragments can be obtained using conventional recombinant and/or enzymatic techniques and can be screened for antigen binding in the same manner as intact antibodies.

[75] A "carbohydrate" refers to a sugar or polymer of sugars. The terms "saccharide,"
polysaccharide," "carbohydrate," and "oligosaccharide" may be used interchangeably. Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule. Carbohydrates generally have the molecular formula CnH2nOn. A
carbohydrate may be a monosaccharide, a disaccharide, trisaccharide, oligosaccharide, or polysaccharide. The most basic carbohydrate is a monosaccharide, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose. Disaccharides are two joined monosaccharides. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose.
Typically, an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units. Exemplary polysaccharides include starch, glycogen, and cellulose. Carbohydrates may contain modified saccharide units such as 2'-deoxyribose wherein a hydroxyl group is removed, 2'-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N-acetylglucosamine, a nitrogen-containing form of glucose (e.g., 2'-fluororibose, deoxyribose, and hexose).
Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.

[76] "Cellular augmentation" broadly refers to the influx of cells or expansion of cells in an environment that are not substantially present in the environment prior to administration of a composition (e.g., pharmaceutical composition) and not present in the composition itself. Cells that augment the environment include immune cells, stromal cells, bacterial and fungal cells.

[77] "Clade" refers to the OTUs or members of a phylogenetic tree that are downstream of a statistically valid node in a phylogenetic tree. The clade comprises a set of terminal leaves in the phylogenetic tree that is a distinct monophyletic evolutionary unit and that share some extent of sequence similarity.

[78] A "combination" of microbes (e.g., bacteria) from two or more microbial strains includes the physical co-existence of the microbes are obtained, either in the same material or product or in physically connected products, as well as the temporal co-administration or co-localization of the two or more strains. In some embodiments, one of the strains is from Prevotella bacteria, e.g., Prevotella histicola bacteria.

[79] The term "decrease" or "deplete" means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000 or undetectable after treatment when compared to a pre-treatment state. Properties that may be decreased include the number of immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites; the level of a cytokine; or another physical parameter (such as ear thickness (e.g., in a DTH animal model) or tumor size (e.g., in an animal tumor model)).

[80] The term "ecological consortium" is a group of bacteria which trades metabolites and positively co-regulates one another, in contrast to two bacteria which induce host synergy through activating complementary host pathways for improved efficacy.

[81] As used herein, "engineered bacteria" are any bacteria that have been genetically altered from their natural state by human activities, and the progeny of any such bacteria.
Engineered bacteria include, for example, the products of targeted genetic modification, the products of random mutagenesis screens and the products of directed evolution.

[82] The term "epitope" means a protein determinant capable of specific binding to an antibody or T cell receptor. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains. Certain epitopes can be defined by a particular sequence of amino acids to which an antibody is capable of binding.

[83] The term "gene" is used broadly to refer to any nucleic acid associated with a biological function. The term "gene" applies to a specific genomic sequence, as well as to a cDNA or an mRNA encoded by that genomic sequence.

[84] "Identity" as between nucleic acid sequences of two nucleic acid molecules can be determined as a percentage of identity using known computer algorithms such as the "FAS TA" program, using for example, the default parameters as in Pearson et al. (1988) Proc.

Natl. Acad. Sci. USA 85:2444 (other programs include the GCG program package (Devereux, J., et al., Nucleic Acids Research 12(I):387 (1984)), BLASTP, BLASTN, FASTA
Atschul, S. F., et al., J Molec Biol 215:403 (1990); Guide to Huge Computers, Mrtin J. Bishop, ed., Academic Press, San Diego, 1994, and Carillo et al. (1988) SIAM J Applied Math 48:1073). For example, the BLAST function of the National Center for Biotechnology Information database can be used to determine identity. Other commercially or publicly available programs include, DNAStar "MegAlign" program (Madison, Wis.) and the University of Wisconsin Genetics Computer Group (UWG) "Gap" program (Madison Wis.)).

[85] "Immunotherapy" is treatment that uses a subject's immune system to treat disease (e.g., immune disease, inflammatory disease, metabolic disease, cancer) and includes, for example, checkpoint inhibitors, cancer vaccines, cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.

[86] The term "increase" means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 2-fold, 4-fold, 10-fold, 100-fold, 101\3 fold, 10A4 fold, 10A5 fold, 101\6 fold, and/or 101\7 fold greater after treatment when compared to a pre-treatment state. Properties that may be increased include the number of immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites; the level of a cytokine; or another physical parameter (such as ear thickness (e.g., in a DTH animal model) or tumor size (e.g., in an animal tumor model).

[87] "Innate immune agonists" or "immuno-adjuvants" are small molecules, proteins, or other agents that specifically target innate immune receptors including Toll-Like Receptors (TLR), NOD receptors, RLRs, C-type lectin receptors, STING-cGAS Pathway components, inflammasome complexes. For example, LPS is a TLR-4 agonist that is bacterially derived or synthesized and aluminum can be used as an immune stimulating adjuvant. immuno-adjuvants are a specific class of broader adjuvant or adjuvant therapy. Examples of STING agonists include, but are not limited to, 2'3'- cGAMP, 3'3'-cGAMP, c-di-AMP, c-di-GMP, 2'2'-cGAMP, and 2'3'-cGAM(PS)2 (Rp/Sp) (Rp, Sp-isomers of the bis-phosphorothioate analog of 2'3'-cGAMP). Examples of TLR agonists include, but are not limited to, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10 and TLRI 1. Examples of NOD agonists include, but are not limited to, N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyldipeptide (MDP)), gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), and desmuramylpeptides (DMP).

[88] The "internal transcribed spacer" or "ITS" is a piece of non-functional RNA
located between structural ribosomal RNAs (rRNA) on a common precursor transcript often used for identification of eukaryotic species in particular fungi. The rRNA of fungi that forms the core of the ribosome is transcribed as a signal gene and consists of the 8S, 5.8S
and 28S regions with ITS4 and 5 between the 8S and 5.8S and 5.8S and 28S regions, respectively.
These two intercistronic segments between the 18S and 5.8S and 5.8S and 28S regions are removed by splicing and contain significant variation between species for barcoding purposes as previously described (Schoch et al Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. PNAS 109:6241-6246. 2012). 18S rDNA is traditionally used for phylogenetic reconstruction however the ITS can serve this function as it is generally highly conserved but contains hypervariable regions that harbor sufficient nucleotide diversity to differentiate genera and species of most fungus.

[89] The term "isolated" or "enriched" encompasses a microbe or other entity or substance that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature or in an experimental setting), and/or (2) produced, prepared, purified, and/or manufactured by the hand of man. Isolated microbes may be separated from at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more of the other components with which they were initially associated. In some embodiments, isolated microbes are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure, e.g., substantially free of other components. The terms "purify," "purifying" and "purified" refer to a microbe or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g., whether in nature or in an experimental setting), or during any time after its initial production. A microbe or a microbial population may be considered purified if it is isolated at or after production, such as from a material or environment containing the microbe or microbial population, and a purified microbe or microbial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or above about 90% and still be considered "isolated." In some embodiments, purified microbes or microbial population are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about

90 PCT/US2020/038335 96%, about 97%, about 98%, about 99%, or more than about 99% pure. In the instance of microbial compositions provided herein, the one or more microbial types present in the composition can be independently purified from one or more other microbes produced and/or present in the material or environment containing the microbial type.
Microbial compositions and the microbial components thereof are generally purified from residual habitat products.
[90] As used herein a "lipid" includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans).

[91] The term "LPS mutant or lipopolysaccharide mutant" broadly refers to selected bacteria that comprises loss of LPS. Loss of LPS might be due to mutations or disruption to genes involved in lipid A biosynthesis, such as 1pxA, 1pxC , and 1pxD.
Bacteria comprising LPS
mutants can be resistant to aminoglycosides and polymyxins (polymyxin B and colistin).

[92] "Metabolite" as used herein refers to any and all molecular compounds, compositions, molecules, ions, co-factors, catalysts or nutrients used as substrates in any cellular or microbial metabolic reaction or resulting as product compounds, compositions, molecules, ions, co-factors, catalysts or nutrients from any cellular or microbial metabolic reaction.

[93] "Microbe" refers to any natural or engineered organism characterized as an archaeaon, parasite, bacterium, fungus, microscopic alga, protozoan, and the stages of development or life cycle stages (e.g., vegetative, spore (including sporulation, dormancy, and germination), latent, biofilm) associated with the organism. In some embodiments, the microbes are bacteria. Examples of gut microbes include: Actinomyces graevenitzii, Actinomyces odontolyticus, Akkermansia mucimphila, Bacteroides caccae, Bacteroides fragilis, Bacteroides putredinis, Bacteroides thetaiotaomicron, Bacteroides vultagus, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bilophila wadsworthia, Blautia, Butyrivibrio, Campylobacter gracilis, Clostridia cluster III, Clostridia cluster IV, Clostridia cluster IX
(Acidaminococcaceae group), Clostridia cluster XI, Clostridia cluster XIII (Peptostreptococcus group), Clostridia cluster XIV, Clostridia cluster XT", Collinsella aerofaciens, Coprococcus, Corynebacterium sunsvallense, Desulfomonas pigra, Dorea formicigenerans, Dorea longicatena, Escherichia coli, Eubacterium hadrum, Eubacterium rectale, Faecalibacteria prausnitzii, Gemella, Lactococcus, Lanchnospira, Mollicutes cluster XVI, Mollicutes cluster XVIII, Prevotella, Rothia mucilaginosa, Ruminococcus callidus, Ruminococcus gnavus, Ruminococcus torques, and Streptococcus.

[94] "Microbiome" broadly refers to the microbes residing on or in body site of a subject or patient. Microbes in a microbiome may include bacteria, viruses, eukaryotic microorganisms, and/or viruses. Individual microbes in a microbiome may be metabolically active, dormant, latent, or exist as spores, may exist planktonically or in biofilms, or may be present in the microbiome in sustainable or transient manner. The microbiome may be a commensal or healthy-state microbiome or a disease-state microbiome. The microbiome may be native to the subject or patient, or components of the microbiome may be modulated, introduced, or depleted due to changes in health state or treatment conditions (e.g., antibiotic treatment, exposure to different microbes). In some aspects, the microbiome occurs at a mucosal surface. In some aspects, the microbiome is a gut microbiome.

[95] A "microbiome profile" or a "microbiome signature" of a tissue or sample refers to an at least partial characterization of the bacterial makeup of a microbiome. In some embodiments, a microbiome profile indicates whether at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more bacterial strains are present or absent in a microbiome.

[96] "Modified" in reference to a bacteria broadly refers to a bacteria that has undergone a change from its wild-type form. Bacterial modification can result from engineering bacteria. Examples of bacterial modifications include genetic modification, gene expression modification, phenotype modification, formulation modification, chemical modification, and dose or concentration. Examples of improved properties are described throughout this specification and include, e.g., attenuation, auxotrophy, homing, or antigenicity. Phenotype modification might include, by way of example, bacteria growth in media that modify the phenotype of a bacterium such that it increases or decreases virulence.

[97] "Operational taxonomic units" and "OTU(s)" refer to a terminal leaf in a phylogenetic tree and is defined by a nucleic acid sequence, e.g., the entire genome, or a specific genetic sequence, and all sequences that share sequence identity to this nucleic acid sequence at the level of species. In some embodiments the specific genetic sequence may be the 16S
sequence or a portion of the 16S sequence. In other embodiments, the entire genomes of two entities are sequenced and compared. In another embodiment, select regions such as multilocus sequence tags (MLST), specific genes, or sets of genes may be genetically compared. For 16S, OTUs that share? 97% average nucleotide identity across the entire 16S or some variable region of the 16S are considered the same OTU. See e.g., Claesson MJ, Wang Q, O'Sullivan 0, Greene-Diniz R, Cole JR, Ross RP, and O'Toole PW. 2010. Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res 38: e200. Konstantinidis KT, Ramette A, and Tiedje JIM. 2006. The bacterial species definition in the genomic era.
Philos Trans R Soc Lond B Biol Sci 361: 1929-1940. For complete genomes, MLSTs, specific genes, other than 16S, or sets of genes OTUs that share? 95% average nucleotide identity are considered the same OTU. See e.g., Achtman M, and Wagner M. 2008. Microbial diversity and the genetic nature of microbial species. Nat. Rev. Microbiol. 6: 431-440. Konstantinidis KT, Ramette A, and Tiedje JIM. 2006. The bacterial species definition in the genomic era. Philos Trans R
Soc Lond B Biol Sci 361: 1929-1940. OTUs are frequently defined by comparing sequences between organisms.
Generally, sequences with less than 95% sequence identity are not considered to form part of the same OTU. OTUs may also be characterized by any combination of nucleotide markers or genes, in particular highly conserved genes (e.g., "house-keeping" genes), or a combination thereof.
Operational Taxonomic Units (OTUs) with taxonomic assignments made to, e.g., genus, species, and phylogenetic clade are provided herein.

[98] As used herein, a gene is "overexpressed" in a bacteria if it is expressed at a higher level in an engineered bacteria under at least some conditions than it is expressed by a wild-type bacteria of the same species under the same conditions. Similarly, a gene is "underexpressed" in a bacteria if it is expressed at a lower level in an engineered bacteria under at least some conditions than it is expressed by a wild-type bacteria of the same species under the same conditions.

[99] The terms "polynucleotide," and "nucleic acid" are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure, and may perform any function. The following are non-limiting examples of polynucleotides:
coding or non-coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), micro RNA (miRNA), silencing RNA
(siRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. A
polynucleotide may be further modified, such as by conjugation with a labeling component. In all nucleic acid sequences provided herein, U nucleotides are interchangeable with T nucleotides.

[100] As used herein, a "biomarker" includes molecules (e.g., mRNA or protein) that have an increase or a decrease in their levels due to a TH2-mediated pathway.
For instance, the levels of one or more such biomarkers may increase in TH2-meidated conditions as compared to their levels in a healthy subject. Some examples of such protein biomarkers include interleukin-4, interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-31, interleukin-33, thymic stromal lymphopoietin, immunoglobulin G1 , immunoglobulin E, immunoglobulin A, and combinations thereof. Some examples of such mRNA
biomarkers include interleukin-4, interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-31, interleukin-33, thymic stromal lymphopoietin, and combinations thereof.

[101] As used herein, a substance is "pure" if it is substantially free of other components. The terms "purify," "purifying" and "purified" refer to Prevotella bacteria preparation or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g., whether in nature or in an experimental setting), or during any time after its initial production. A
Prevotella bacteria preparation or composition may be considered purified if it is isolated at or after production, such as from one or more other bacterial components, and a purified microbe or microbial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or above about 90% and still be considered "purified." In some embodiments, purified Prevotella bacteria are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. Prevotella bacteria compositions or preparations are, e.g., purified from residual habitat products.

[102] As used herein, the term "purified Prevotella bacteria" or "Prevotella bacteria composition" refers to a preparation that includes Prevotella bacteria that have been separated from at least one associated substance found in a source material (e.g., separated from at least one other bacterial strain) or any material associated with the Prevotella bacteria in any process used to produce the preparation. It also refers to a composition that has been significantly enriched or concentrated. In some embodiments, the Prevotella bacteria are concentrated by 2 fold, 3-fold, 4-fold, 5-fold, 10-fold, 100-fold, 1000-fold, 10,000-fold or more than 10,000 fold.
In certain embodiments, the Prevotella bacteria composition can be a pharmaceutical composition.

[103] "Residual habitat products" refers to material derived from the habitat for microbiota within or on a subject. For example, fermentation cultures of microbes can contain contaminants, e.g., other microbe strains or forms (e.g., bacteria, virus, mycoplasm, and/or fungus). For example, microbes live in feces in the gastrointestinal tract, on the skin itself, in saliva, mucus of the respiratory tract, or secretions of the genitourinary tract (i.e., biological matter associated with the microbial community). Substantially free of residual habitat products means that the microbial composition no longer contains the biological matter associated with the microbial environment on or in the culture or human or animal subject and is 100% free, 99%
free, 98% free, 97% free, 96% free, or 95% free of any contaminating biological matter associated with the microbial community. Residual habitat products can include abiotic materials (including undigested food) or it can include unwanted microorganisms.
Substantially free of residual habitat products may also mean that the microbial composition contains no detectable cells from a culture contaminant or a human or animal and that only microbial cells are detectable. In one embodiment, substantially free of residual habitat products may also mean that the microbial composition contains no detectable viral (including bacteria, viruses (e.g., phage)), fungal, mycoplasmal contaminants. In another embodiment, it means that fewer than 1x102%, 1x10-3%, 1x10-4%, 1x10-5%, 1x10-6%, 1x10-7%, 1x10-8% of the viable cells in the microbial composition are human or animal, as compared to microbial cells. There are multiple ways to accomplish this degree of purity, none of which are limiting. Thus, contamination may be reduced by isolating desired constituents through multiple steps of streaking to single colonies on solid media until replicate (such as, but not limited to, two) streaks from serial single colonies have shown only a single colony morphology. Alternatively, reduction of contamination can be accomplished by multiple rounds of serial dilutions to single desired cells (e.g., a dilution of 10-8 or 10-9), such as through multiple 10-fold serial dilutions. This can further be confirmed by showing that multiple isolated colonies have similar cell shapes and Gram staining behavior.
Other methods for confirming adequate purity include genetic analysis (e.g., PCR, DNA
sequencing), serology and antigen analysis, enzymatic and metabolic analysis, and methods using instrumentation such as flow cytometry with reagents that distinguish desired constituents from contaminants.

[104] As used herein, "specific binding" refers to the ability of an antibody to bind to a predetermined antigen or the ability of a polypeptide to bind to its predetermined binding partner. Typically, an antibody or polypeptide specifically binds to its predetermined antigen or binding partner with an affinity corresponding to a KD of about 10 M or less, and binds to the predetermined antigen/binding partner with an affinity (as expressed by KD) that is at least 10 fold less, at least 100 fold less or at least 1000 fold less than its affinity for binding to a non-specific and unrelated antigen/binding partner (e.g., BSA, casein).
Alternatively, specific binding applies more broadly to a two component system where one component is a protein, lipid, or carbohydrate or combination thereof and engages with the second component which is a protein, lipid, carbohydrate or combination thereof in a specific way.

[105] "Strain" refers to a member of a bacterial species with a genetic signature such that it may be differentiated from closely-related members of the same bacterial species. The genetic signature may be the absence of all or part of at least one gene, the absence of all or part of at least on regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the absence ("curing") of at least one native plasmid, the presence of at least one recombinant gene, the presence of at least one mutated gene, the presence of at least one foreign gene (a gene derived from another species), the presence at least one mutated regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or a combination thereof. Genetic signatures between different strains may be identified by PCR
amplification optionally followed by DNA sequencing of the genomic region(s) of interest or of the whole genome. In the case in which one strain (compared with another of the same species) has gained or lost antibiotic resistance or gained or lost a biosynthetic capability (such as an auxotrophic strain), strains may be differentiated by selection or counter-selection using an antibiotic or nutrient/metabolite, respectively.

[106] The terms "subject" or "patient" refers to any mammal. A subject or a patient described as "in need thereof- refers to one in need of a treatment (or prevention) for a disease.
Mammals (i.e., mammalian animals) include humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents).

The subject may be a human. The subject may be a non-human mammal including but not limited to of a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee. The subject may be healthy, or may be suffering from a condition at any developmental stage, wherein any of the stages are either caused by or opportunistically supported of a condition-associated or causative pathogen, or may be at risk of developing a condition, or transmitting to others a condition-associated or condition-causative pathogen. In some embodiments, a subject has a TH2-mediated condition. In some embodiments, a subject has atopic dermatitis. In some embodiments, a subject has asthma. In some embodiments, a subject has a food allergy. In some embodiments, the subject has undergone a therapy for their condition.

[107] As used herein, the term "treating" a disease in a subject or "treating" a subject having or suspected of having a condition refers to subjecting the subject to a pharmaceutical treatment (e.g., a pharmaceutical composition), e.g., the administration of one or more agents (e.g., pharmaceutical compositions), such that at least one symptom of the condition is decreased or prevented from worsening. Thus, in one embodiment, "treating" refers inter alia to delaying progression, expediting remission, inducing remission, augmenting remission, speeding recovery, increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof.
Bacteria

[108] In certain aspects, provided herein are bacterial compositions, such as pharmaceutical compositions, comprising certain bacteria and methods of using such bacterial compositions, such as pharmaceutical compositions to treat and/or prevent TH2-mediated conditions.

[109] In certain embodiments, the pharmaceutical compositions provided herein comprise bacteria of the genus Prevotella. In some embodiments, the bacteria of the genus Prevotella are of the species Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccahs, Prevotella copri, Prevotella dentalis, Prevotella dent/cola, Prevotella disiens, Prevotella histicola, Prevotella melanogenica, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pa/lens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoo gleoformans, Prevotella veroralis, and/or a combination thereof.

[110] In some embodiments, the bacteria of the genus Prevotella is of the species Prevotella histicola.

[111] In some embodiments, the bacteria of the genus Prevotella is a strain comprising at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.1% sequence identity, at least 99.2% sequence identity, at least 99.3% sequence identity, at least 99.4% sequence identity, at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7%
sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to a nucleotide sequence (e.g., the genomic sequence, the 16S sequence, and/or the CRISPR
sequence) of the Prevotella Strain B 50329. In some embodiments, the bacteria of the genus Prevotella is Prevotella Strain B 50329 (NRRL accession number B 50329). As used herein, the term "Prevotella Strain B 50329" includes both the strain deposited under NRRL
accession number B 50329 and strains cloned and/or derived from the deposited strain.

[112] Prevotella histicola Strain B can be cultured according to methods known in the art. For example, Prevotella histicola can be grown in ATCC Medium 2722, ATCC
Medium 1490, or other medium using methods disclosed, for example in Caballero et al., 2017.
"Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium" Cell Host & Microbe 21:592-602, which is hereby incorporated by reference in its entirety.

[113] In some embodiments, the Prevotella bacteria is a strain of Prevotella bacteria comprising one or more (e.g., 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or more) proteins listed in Table 1 and/or one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or more) genes encoding proteins listed in Table 1. In some embodiments, the Prevotella bacteria comprises all of the proteins listed in Table 1 and/or all of the genes encoding the proteins listed in Table 1.
Table 1: Exemplary Prevotella proteins Seq. Name Uniprot ID
Amino Acid Sequence ID. No.
MNLKTFTKTVLCFALFAVSAITAKAADHLAIVGEAVWGGWD
LVKATAMVKSPNNPDVFMATVHLNAGKGFKFLTEREWGKL
EYRSGASDVVLKSGIRYKLYASIGASEDGKFKVSESANYEIICDL
ARKTVEVKKVAYQAKEIRYAALWMIGDATAGDWDYNNGVL
LSQDSGNPTCYTATVELKEGEFKFTTNKQWGYDHSVYIFRDV
NDQNKIVFGGEDNKWRITEDGMYNVTVDVPTKTISIKQIDD
PAGHKPQFGNDVILVGDATIAGWNLDNAIYLEHTGQAGRVF
KTTTYLEAGKGFKFLSMLSYDDIDYRPANNTVLNPGVPGTFV
Cluster: PSLPSSTDTKFSVERSGNYDIVCNMNNRTVVVTLSENQVLVN
1 Uncharacterized G6ADE1 YPALWLIGSATSAGWNPGKAVELKRSEADPAVYTARVQLKK
protein GEFKILTSKNVGFDQPTYYRDSTNEHRIVFGVDGDEVAKKDC
KWTLSENAEGTYDVTVDIEAMTIFCDKVNMDEPSVESTDKEL
ILIGDATYSAWDLPKSIVMTPVGPTTFKAVTHLEAGKEFKFLT
ELAWKRYEYRAESLRKELQEGSMSMLVPYRYTNDKDDKDHD
FKFVVKESGNYEIVCDLYIPALIIRKVRYQDTPVTYSSLWIVGSA
TPGGWTIERGIKMTQDENYPTKFTAKANLVPGELKFATNKFA
DFTQDFFFRGKDDYTAVLGGNDNKWNITEAGTYSVTIDVAS
KRVTITKPARNAPTGISTVDSSDEAPAEYFTLNGIKVTTPSSGIY
IKRQGGRTTKVVMK
MDTYQILDIIGCIVGLIYIYQEYKASIWLWMTGIIMPVIYMFVY
Nicotinamide_ribo YEAGLYADFGMQIYYTLAAIYGYLYWKLGKKKGTEDKEI PITH
2 side_transporter_ P24520 FPRRYIIPAIIVFFVLWIALYYILICFTNSTVPVLDSFGNALSFIGL
PnuC WALAKKYLEQWWIWIVVDAELSALYIYKGIPFTAMLYALYTVI
AVAGYFKWRRYIKQQK
MRVRLYKNILLFLFLWVNTLACVSADTSRTVESQPIENGLIITE
SKGWLETIYAKWKPVAEADGYYVYVKGGQYADYSKVDSELIR
Pectate trisacchar VYNGYVRVDIPGLKAGTYSLKIVAVKGGKETQSSEVTGLKVLN

ide-Iyase Q8GCB2 YVREGFAHKNYSGVGAYNDDGTLKSGAVVIYVNKDNAKTVS
AHLGKTTFIGLQAILNAYQKGNITTPLSVRILGLLRNGDTDTFG
SSTEGIQIKGKQADSEMNITIEGIGEDASIYGFGFLVRNAKSVE
FRNLGIMRAMDDGVSLDTNNSNIWIHHMDLFYGKASGGD

HIKGDGSIDVKTDSKYVTIDNCHFWDTGKTSMCGMKKETGP
NYITYHHNWFDHSDSRHARVRTMSVHLWNNYYDGCAKYGI
GATMGCSVFSENNYFRATKNPILISKQGSDAKGTGKFSGEPG
GMVKEYGSLFTEKGAESTYTPISYADNNSSFDFYHAISRNEKV
PASVKTLNGGNIYNNFDTDAALMYSYTPDATALVPSQVTGFY
GAGRLNHGSLQFKFNNAVEDTNSTPIPALEALIDAYSGK
MKYNIAYCIEGFYNHGGMERILSVCANLLSDIYSITIIVANQRG
REHAYNLAQNVNVVDLGVSCKNYKEEYKKSLTRYLQDHQFS
VVISLAGLELFFLPQIKDGSKKVMWFHFAFDVSKMFLSERFH
GWKLNLLYYIHTIRRIYFAKKFDTIVVLSKSDCDSWSRFCNNVK
Glycosyltransferas eGtfl _ DKHPDWHLDIFGEGPDRLELQHQIDRKGLHDKVRLCGVTKQ
IEEEYGKHSIYVMSSRAEGFPLALLEASSCGLPMISFNCHQGP
NEIIQEGENGFLVDKVGDIYTLSDRICKLIEDNNLRNMMGKK
ALDSSFRFEGEVIKKDWISLLKQLI
MKRLFFMFLFLGTITMNSLAQEEKPIKYETKNFSLPDKMPLYP
Cluster: Protein GGDGALRAFLSLNLHYPEKAQAFGVEGRSLMKFCVSSDGSIK

TonB DISAVDCKITNYNRTEFNKLPLSKQESLKKECAKAFAKEAARVI
RLMPKWEPAELNGKKMNVYYSLPFTFKLR
MNYPLFIARKIYNGGDRTRKVSKPAIRIATIGVAIGLAVMIISV
GVVLGFKHTIRNKVVGFGSDITVANFLTLQSSEQYPIQITDSLV
KSLQITPGIKHVQRYDYTQGILKTDNDFLGVLLKGVGPDFDST
FIHENMVEGSLPHFHDNESQQKIVISKTIADKLNLKVGQRIFA
Cluster:
YFINKQGVRTRKFTITGIYATNMKQFDSQICFTDIYTTNKLNG
6 Uncharacterized G6AEN6 WEPDQYSGAELQVDNFSQLTPISMRVLNKVKNTVDHYGGT
protein YSSENIIEQNPQIFSWLDLMDMNVWIILALMISVAGVTMISG
LLIIILERTQMIGILKALGSRNRQIRHIFLWFATFIIGKGLLWGNI
IGLGCILFQSWTGLVKLDPQTYYVNTVPVEINIPLIIALNMVT
MLVCLVILIAPSYLISHIHPAKSMHYE
MEDKFIYTDKERKLSYQILDELKDTLDKSFLENDLPMLQVQLK
DSVAKNTIHRNVFGLNPILCSLQTAAIAVKDIGLKRDSVIAILLH
QSVQDGYITLEDIDNRFGKSVAKIIHGLIRIQTLYQKNPIIESEN
Bifunctional_(p)pp FRNLLLSFAEDMRVILIMIADRVNLMRQIRDAEDKEAQHKVA
7 Gpp_synthase/hy P9WHG9 EEASYLYAPLAHKLGLYQLKRELEDLSLKYLEHDAYYLIKDKLN
drolase_RelA ATKASRDAYINQFIAPVRERLTAGGLRFHIKGRTKSIHSIWQK
MKKQKCGFEGIYDLFAIRIILDAPLEKEKIQCWQAYSIVTDMY
QPNPKRLRDWLSVPKSNGYECLHITVLGPEKKWVEVQIRTER
MDEIAEHGLAAHWRYKGIKEEGGLDDWLASIRAALEAGDNL

EVMDQFKSDLYEKEIYVFTPKGDLLKFPKGATILDFAYHIHSKV
GNQCVGGKINAKNVSLRTELHSGDTVEILTSATQKPKAEWLK
IVKSSRAKAKIRLALKETQIKDGLYAKELLERRFKNKKIEIEESTM
GHLLRKLGFKEVSEFYKQVADEKLDPNYIIEEYQKVYNHDHNL
NQPKETESAENFEFENPTNEFLKKNDDVLVIDKNLKGLDFSLA
KCCHPIYGDPVFGFVTVNGGIKIHRTDCPNAPEMRKRFGYRI
VKARWSGKGSSQYAITLRVIGNDDIGIVSNITNVISKDEKIVM
RSINIDSHDGLFSGNLVVLLDDNSKLNMLIKKLRTVKGVKQVT
RI
MKRRIFLFVALSVSIVILFGLNLIIGSVHIPLSDILTILSGSFTGKES
WRFIIWDSRLPQALTAMLCGSSLAVCGLMLQTAFRNPLAGP
Vitamin_B12_imp DVFGISSGASLGVALVMLLLGGTVETSMFTASGFLAILIVAFA
ort_system_perm GAILVTAFILFLSSVVRNSVLLLIVGIMVGYVASSAVTLLNFFSS

ease_protein_Btu EDGVKGYIVWGMGNFGGVSMSHIPLFAFLCLAGIIASFLLVK
C
PLNILLLGPQYAESLGISIRRIRNILLVVVGILTAVTTAFCGPISFI
GLAAPHVARLLFRTENHQKLLPGTLLVGTVVALLCNLICFLPRE
SGMIPLNAVTPLIGAPIIIYVIMKRH
MKLENKEFGFDSFATEMARLKNEKHFDYLVTVVGEDFGTEE
GLGCIYILENTSTHERCSVKQLAKKVGEEFVIPSVIKLWADADL
LEREVYDFYGIKFLGHPDMRRLFLRNDFKGYPLRKDYDMDPA
KNMYTTEDDVELDTTTEWNLDKNGELVGTQHALFTDDNFV
VNIGPQHPSTHGVLRLQTVLDGETVTNIYPHLGYIHRGIEKLC
NADH-EQFTYPQTLALTDRMNYLSAMMNRHALVGVIEEGMGIELSE
quinone_oxidored uctase_subunit_C
HVLNVMEETTGGRLIQNYYRIGGLQADIDPNFVSNVKELCKY
/D
LRPMIQEYVDVFGDNVITHQRFEGVGVMDEKDCISYGVTGP
AGRASGWKNDVRKYHPYAMYDKVNFEEITLTNGDSMDRYF
CHIKEIYQSLNIIEQLIDNIPEGEFYIKQKPIIKVPEGQWYFSVEG
ASGEFGAYLDSRGDKTAYRLKFRPMGLTLVGAMDKMLRGQ
KIADLVTTGAALDFVIPDIDR
FKBP- MRTSTQSKDMGKKQEYKLRNEEFLHNISKKDSIKTLPHGIFYEI
type_peptidyl- P45523 IKEGSGEGTVQPRSIVICNYRGSLISGQVFDDSWQKPTPEAFR
prolyl_cis- LNELITGLQIALCAMHKGDSWRIYIPYQEGYGSKRNADIPAFS
trans_isomerase TLIFDIELINIA
Putative_acetolact MADNKIAKESVKREVIAGERLYTLLVYSENVAGVLNQIAAVFT
11 ate_synthase_sma P9WKJ3 RRQVNIESLNVSASSIEGIHKYTITAWSDAATIEKITKQVEKKID
Il_subunit VIKADYYEDSDLFIHEVGLYKIATPILLENAEVSRAIRKRNARM

MEVNPTYSTVLLAGMTDEVTALYHDLKNFDCLLQYSRSGRV
AVTRGFSEPVSDFLKSEEESSVL
MKKKVKIGLLPRVIIAILLGIFFGYFMPTPLARVFLTFNGIFSQFL
GFMIPLIIIGLVTPAIADIGKGAGKLLLVTVIIAYVDTVVAGGLA
YGTGLCLFPSMIASTGGAMPHIDKATELAPYFSINIPAMADV
MSGLVFSFMLGLGIAYGGLTATKNIFNEFKYVIEKVIAKAIIPLL
Serine/threonine 12 ¨ POAGE4 PLYIFGVFLNMAHNGQAQQILLVFSQIIIVILVLHVFILVYQFCI
transporter_SstT
AGAIIRRNPFRLLWNMMPAYLTALGTSSSAATIPVTLEQTMK
NGVGKEIAGFVVPLCATIHLSGSAMKITACALTICLLVGLPHDP
ALFIYFILMLSIIMVAAPGVPGGAIMAALAPLASILGFNSEAQA
LMIALYIAMDSFGTACNVTGDGAIALVVNKMFGKKER
MKKLLLLVCAAVMSLSASAQAGDKALGAQLVFGSETNSLGF
Cluster:
GVKGQYYFTDHIRGEGSFDYFLKNKGISMWDINANVHYLFD
13 Uncharacterized G6AJO7 VADKFKVYPLAGLGYTNWSYKYEYAGAPVVEGSDGRLAVNL
protein GGGVEYELTKNLNVNAEAKYQIISNYNQLVLGVGVAYKF
Heterocyst_differ

114 entiation_ATP- P22638 MHFYCTKSSLDTMSERYVKRMIAKLASQGKTVISIAHRFSTIM
binding_protein DAKHIILLAKGKVVAEGTHQELLKTSEDYRKLWSDQNDEID
MKNVYFLSDAHLGSLAIAHRRTQERRLVRFLDSIKHKASAVYL
LGDMFDFWDEYKYVVPKGFTRFLGKVSELTDMGVEVHFFTG
UDP-2,3- NHDLWTYGYLEEECGVILHRKPVTMEIYGKVFYLAHGDGLGD
15 diacylglucosamine Q912V0 PDPMFQFLRKVFHNRVCQRLLNFFHPWWGMQLGLNWAK
_hydrolase KSRLKRADGKEMPYLGEDKEYLVRYTKDYMRSHKDIDYYIYG
HRHIELDLTLSGKVRMULGDWIWQFTYAVFDGEHMFLEEYI
EGESKP
MNSKQNDNYDVIIIGGGITGAGTARDCALRGLKVLLVEKFDF
TNGATGRNHGLLHSGARYAVTDPESATECIKENMVLRRIAKH
CIEETDGLFITLPEDDINYQKTFVEACARAGISANIISPEEALRL
Anaerobic_glycero DPSVNPDLLGAVRVPDASVDPFHLTTANVLDARQHGADVLT

YHEVVAILTSNGRVEGVRLRNNHTGEEIEKHAVLVINAAGIW
16 phosphate_dehyd P0A9C0 GHDIAKMADIKINMFPAKGTLLVFGHRVNKMVINRCRKPAN
rogenase ADILVPDDAVCVIGTTSDRVPYDTVDNLKITSEEVDTLIREGEK
LAPSLATTRILRAYAGVRPLVAADNDPTGRSISRGIVCLDHEKR
DGLTGMITITGGKMMTYRLMAEQATDLACKKLGINKTCETA
TTPLPGTAGKDSDNPHHTYSTAHKAAKGRQGNRVKEIDERT
EDDRALICECEEVSVGEAKYAIEELHVHDLLNLRRRTRVGMGT

CQGELCACRAAGVMCENGVKVDKAMTDLTKFINERWKGM
RPVAWGSTLDEAQLTTIIYQGLCGLGI
MRYDTIIIGGGLSGLTAGITLAKAGQKVCIVSAGQSSLHFHSG
SFDLLGYDADGEVVTHPLQAIADLKAEHPYSKIGISNIEHLASQ
AKTLLCEAGISVMGNYEQNHYRVTPLGTLKPAWLTTEGYAMI
Anaerobic_glycero DDPEILPWKKVELLNIQGFMDFPTQFIAENLRMMGVECQIK

phosphate_dehyd GDPDALLLPAVLGFSNAESLDEMKQWIKKPVQYIATLPPSVS
rogenase GVRTTILLKRLFAQAGGTLLIGDSATTGQFSGNHLVSITTDHLP
DEKLYADHFILASGSFMSHGIRSNYAGVYEPVFKLDVDAAEK
RDDWSVTNAFEAQPYMEFGVHTDKDFHATKDGKNIENLYAI
GSVLSGHNSIKHADGTGVSLLTALYVAKKITGKG
MAEGIQLKNISGNNLEQCLKCSICTAYCPVSAVEPKYPGPKQS
GPDQERYRLKDSKFFDEALKMCLNCKRCEVACPSGVRIADIIQ
ASRITYSTHRPIPRDIMLANTDFVGTMANMVAPIVNATLGLK
Anaerobic_glycero PVKAVLHGVMGIDKHRTFPAYSSQKFETWYKRMAAKKQDS

phosphate_dehyd CCGVALIANGLSGQARRQGKVNIRSIRKAAEQNRIVLTTSSTC
rogenase TFTMRDEYEHLLDIKTDDVRENITLATRFLYRLIEKGDIKLAFRK
DFKMRTAYHSACHMEKMGWIlYSTELLKMIPGLELIMLDSQ
CCGIAGTYGFKKENYQRSQEIGEGLFKQIKELNPDCVSTDCET
CKWQIEMSTGYEVKNPISILADALDVEETIKLNQ
MMIKNIVLSIPISLIIYLNHLIMEYSMTTQFLMELIGTLILVLFGD
GVCACVTLNKSKGQKAGWVVITIAWGLAVCMGVLVAGPYT
GAHLNPAVSIGLAVAGMFPWSSVPYYIVAQMIGGFLGGLLV
Glycerol_uptake_f acilitator_protein VLVFIIISFSVDGNTGDAEHFKFGLAALGPIPVTLLIIALGMSLG
GTTGYAMNPARDLSPRLAHAVCMKGDNDWSYSWIPVLGPI
IGAIIAGFCGAALLLV
MSEKIIPSNEPAQAASEPIKASYTEYTVIPSQGYCQFVKCKKGD
QPVVLKGLKEAYRERVLLRNALKREFKQCQRLNHPGIVRYQG
Serine/threonine-LVDVEGYGLCIEEEYVDGRTLQAYLKESHTDDEKITIVNQIADA
20 protein_kinase_St Q97PA9 LRYAHQQGVAHRNLKPSNILITKQGDHVKLIDFNVLSLDDVK
kP PTADTTRFMAPELKDETMTADGTADIYSLGTIMKVMGLTLA
YSEVIKRCCAFKRSDRYSDIDEFLADFNHDGSSFSMPKIGKGT
VVIGFIAVVVIALAALAYNYGGALVDQVGKIDVTSIFKSDAETA
PEDSAMVKSVEQNNNDSVADEAPATGKLAFMNTMKPALYK

DLDRLFAKHSDDRAKLNRAIKVYYRGLIQANDTLDNEQRAEL
DRVFGNYVKQKKAALK
Cluster: D-alanyl-21 D-alanine G6AHI1 MLVAQLFVGVLQAQKPVQNRRQAVGQSMERQGLVNVKAV
dipeptidase VPSIKVALMYARTDNFCHRMALS
MITGLVIIQLLIVLALIFIGARVGGIGLGIYGMIGVFILVYGFGLA
PGSAPIDVMMIIVAVITAASALQASGGLEYLVGVAAKFLQKH
PDHITYFGPITCWLFCVVAGTAHTSYSLMPIIAEIAQTNKIRPE
RPLSLSVIAASLGITCSPVSAATAALISQDLLGAKGIELGTVLMI
Anaerobic_C4- CIPTAFISILVAAFVENHIGKELEDDPEYKRRVAAGLINPEAACE
22 dicarboxylate_tra POABN5 EVQKAENEHDPSAKHAVWAFLFGVALVILFGFLPQLRPEGVS
nsporter_DcuA MSQTIEMIMMSDAALILLVGKGKVGDAVNGNIFKAGMNAV
VAIFGIAWMGNTFYVGNEKILDAALSSMISSTPILFAVALFLLSI
MLFSQAATVTTLYPVGIALGINPLLLIAMFPACNGYFFLPNYP
TEVAAIDFDRTGTTRVGKYVINHSFQIPGFITTIVSILLGVLMV
QFFR
MRILKITFVTVLALVMSTVVFAQKPKIRIIATGGTIAGVSASAT
SSAYGAGQVGVQTLIDAVPQIKDIADVSGEQLVNIGSQDMN
DEVWLKLAKRINDLLNKEGYDGVLITHGTDTMEETAYFLSLTV
HTDKPVVMVGSMRPSTAISADGPANLYNGICTLVDPSSKGH
23 L-asparaginase_2 P00805 GVMVCMNNELFEAKSVIKTHTTDVSTFKGGLYGEMGYVYN
GKPYFLHKPVAKQGLTSEFNVDNLTSLPKVGIVYGYANCSPLP
IQAFVNAKFDGIVLAGVGDGNFYKDVFDVALKAQNSGIQIVR
SSRVPFGPTNLNGEVDDAKYHFVASLNLNPQKARVLLMLALT
KTKDWQKIQQYFNEY
MALACAMTMSASAQMGTNPKWLGDAIFYQIYPSSYMDTD
GNGIGDLPGITQKLDYIKSLGVNAIWLNPVFESGWFDGGYDV
IDFYKIDPRFGTNTDMVNLVKEAHKRGIKVCLDLVAGHTSTK
CPWFKESANGDRNSRYSDYFIWTDSISEADKKEIAERHKEAN
PASSTHGRYVEMNAKRGKYYEKNFFECQPALNYGFAKPDPN

Trehalose_synthas P9WQ19 QPWEQPVTAPGPQAVRREMRNIMAFWFDKGVDGFRVDM
e/amylase_TreS ASSLVKNDWGKKEVSKLWNEMREWKDKNYPECVLISEWSD
PAVAIPAGFNIDFMIHFGIKGYPSLFFDRNTPWGKPWPGQDI
SKDYKFCYFDKAGKGEVKEFVDNFSEAYNATKNLGYIAIPSAN
HDYQRPNIGTRNTPEQLKVAMTFFLTMPGVPFIYYGDEIGM
KYQMDLPSKEGSNERAGTRTPMQWTSGPTAGFSTCNPSQL
YFPVDTEKGKLTVEAQQNDPRSLLNYTRELTRLRHSQPALRG

NGEWILVSKESQPYPMVYKRTSGGETVVVAINPSDKKVSANI
AHLGKAKSLIMTGKASYKTGKTEDAVELNGVSAAVFKIAE
MNIAVIFAGGSGLRMHTKSRPKQFLDLNGKPIIIYTLELFDNH
PGIDAIVVACIESWIPFLEKQLRKFEINKVVKIVPGGESGQASIY
Ribito1-5-NGLCAAEAYIKSKNVASEDTTVLIHDGVRPLITEETITDNINKV
25 phosphate_cytidyl .. Q720Y7 AEVGSCITCIPATETLVVKQHDGSLEIPSRADSLIARAPQSFLLS
yltransferase DILTAHRRAIDEKKNDFIDSCTMMSHYGYRLGTIIGPMENI KIT
TPTDFFVLRAMVKVHEDQQIFGL
MTEKKSVSIVLCTYNGTKYLQEQLDSILAQTYPLHEIIIQDDGS
TDNTWQILEKYEEKYPLIHIYHNEGTHGVNANFLSAMHRTTG
UDP-Glc:alpha-D- DFIAIADQDDIWETDKIANQMTTIGNKLLCSGLTRPFSSDGSF
G1cNAc- AYFDNRPRNVSIFRMMFLGLPGHTMLFRRELLRMMPPVTH

diphosphoundeca SFFNVSLYDAALSILAASHDSIAFCNKVLVNFRRHADATTYND
prenol YSRSLPSWQNGLYELLWGLRHYHQARSIALPIYRGKLALMEGI
TTNYHDFIEAKAIMRLETQKGLWAFLRLQYLLTKNHQRLFQT
SGGSFIKMIRAWLYPVMQLYMYHHALRRCK
MESFIIEGGHRLSGTIAPQGAKNEALEVICATLLTTEEVIIRNIP
NILDVNNLIKLLQDIGVKVKKLGANDFSFQADEVKLDYLESIDF
VKKCSSLRGSVLMIGPLLGRFGKATIAKPGGDKIGRRRLDTHF
LGFKNLGARFVRIEDRDVYEIQADKLVGDYMLLDEASVTGTA
NIIMSAVMAEGTTTIYNAACEPYIQQLCHLLNAMGAKITGIAS
UDP-N-acetylglucosamine DVSIPNLGULDTFRRLGVQIIEDEDDLIIPRQDHYVIDSFIDGTI
MTISDAPWPGLTPDLISVLLVVATQAQGSVLFHQKMFESRLF
FVDKLIDMGAQIILCDPHRAVVVGHDHAKKLRAGRMSSPDI
RAGIALLIAALTAEGTSRIDNIAQIDRGYENIEGRLNALGAKVQ
RVEIC
MERSGNFYKAIRLGYILISILIGCMAYNSLYEWQEIEALELGNK
KIDELRKEINNINIQMIKFSLLGETILEWNDKDIEHYHARRMA
MDSMLCRFKATYPAERIDSVRHLLEDKERQMCQIVQILEQQ
QAINDKITSQVPVIVQKSVQEQPKKSKRKGFLGIFGKKEEAKP
Sensor_protein_E
TVTTTMHRSFNRNMRTEQQAQSRRLSVHADSLAARNAELN
28 vgS P30855 RQLQGLVVQIDGKVQTDLQKREAEITAMRERSFIQIGGLTGF
VILLLVISYIIIHRNANRIKRYKQETADLIERLQQMAKRNEALITS
RKKAVHTITHELRTPLTAITGYAGLIQKNFNADKTGMYIRNIQ
QSSDRMREMLNTLLSFFRLDDGKEQPNFSTCRISSIAHTLESE
FMPIAINKGLALTVTNHTDAVVLTDKERILQIGNNLLSNAIKFT
ENGAVSLTMGYDNGMLKLIVKDTGSGMTEEEQQRVFGAFE

RLSNAAAKDGFGLGLSIVQRIVTMLGGTIQLKSEKGKGSRFTV
EIPMQSAEELPERINKTQIHHNRTLHDIVAIDNDKVLLLMLKE
MYAQEGIHCDTCTNAAELMEMIRRKEYSLLLTDLNMPDING
FELLELLRTSNVGNSRIIPIIVTTASGSCNREELLERGFSDCLLKP
FSISELMEVSDKCAMKGKQNEKPDFSSLLSYGNESVMLDKLI
AETEKEMQSVRDGEQRKDFQELDALTHHLRSSWEILRADQP
LRELYKQLHGSAVPDYEALNNAVTAVLDKGSEIIRLAKEERRK
YENG
MKRSRFYITVGLILSLTLLMSACGQKKAKDGRTDTPTSGTIKFA
SDESFSPIVEELLQNYQFRYPQAHLLPIYTDDNTGMKLLLDQK
VNLFITSHAMTKGEDAILRGKGPIPEVFPIGYDGIAFIVNRSNP
Phosphate-DSCITVDDVKKILQGKIAKWNQLNPKNNRGSIEVVFDNKASA
29 binding_protein_P Q7A5Q2 TLHYVVDSILGGKNIKSENIVAAKNSKSVIDYVNKTPNAIGVIG
stS
SNWLNDHRDTTNTTFKKDVTVASISKATVASPSNSWQPYQA
YLLDGRYPFVRTIYALLADPHKALPYAFANYIANPIGQMIIFKA
GLLPYRGNINIREVEVKNQ
MAGTKRIKTALISVFHKDGLDDLLKKLDEEGVQFLSTGGTQQ
Bifunctional_purin FIESLGYECQKVEDVTSYPSILGGRVKTLHPKIFGGILARRDNEE
30 e_biosynthesis_pr P9WHM7 DQKQMVEYTIPAIDLVIVDLYPFEQTVASGASAQDIIEKIDIGG
otein_PuTH ISLIRAGAKNFKDVVIVPSKAEYPVLLQLLNTKGAETEIEDRKM
FAERAFGVSSHYDTAIHSWFAAE
MEEEKGGRIGQRPYILKIITERNYIIIIDMKKAKILLFVTALVAVL
TSCGGGQKGLPTSDEYPVITIGASNAQLKTTYPATIKGVQDVE
VRPKVSGFITKLNIHEGEYVHAGQVLFVIDNSTYQAAVRQAQ
AQVNSAQSAVAQAKANVVQANASLNSANAQAATSRLTYN
NSQNLYNNKVIGDYELQSAKNTYETAQASVRQAQSGIASAQ
Multidrug_efflux_ AAVKQAEAGVRQAQAMLSTAKDNLGFCYVKSPASGYVGSLP
31 pump_subunit_Ac POAE06 FKEDALVSASSAQPVTTISNTSTIEVYFSMTEADVLKLSRTDDG
TA
LSNAIKKFPAVSLLLADGSTYNHEGAIVKTSGMIDATTGTINVI
ARFPNPEHLLKSGGSGKIVIAKNNNRALLIPQEAVTQVQNKM
FVYKVDAKDKVHYSEITVDPQNDGINYIVTSGLKMGERIVSK
GVSSLEDGAKIKALTPAEYEEAIKKAEKLGENQSSASGFLKTM
KGDSK
MAKRRNKARSHHSLQVVTLCISTAMVLILIGMVVLTVFTSRN
Cell division_prot LSSYVKENLTVTMILQPDMSTEESAALCQRIRSLHYINSLNFIS
_ 32 ein FtsX Q81X30 KEQALKEGTRELGANPAEFAGQNPFTGEIELQLKANYANNDS
_ IKNIERELRTYRGVSDITYPQNLVESVNHTLGKISLVLLVIAILLTI
VSFSLMNNTIRLSIYARRFSIHTMKLVGASWGFIRAPFLRRAV

MEGLVSALLAIAVLGVGLCLLYDYEPDITKVLSWDVLVITAGV
MLAFGVLIATFCSWLSVNKFLRMKAGDLYKI
MKLSDLKTGETGVIVKVLGHGGFRKRIIEMGFIQGKQVEVLL
NAPLRDPVKYKIMGYEVSLRHSEADQIEVISAEEARQLEQAKA
DNEPQQGALSNNIPDESDHALTPFELTDAANRKSKVINVALV
GNPNCGKTSLFNFASGAHERVGNYSGVTVDAKVGRANYEG
YEFHLVDLPGTYSLSAYSPEELYVRKQLVEKTPDVVINVIDASN
LERNLYLTTQLIDMHVRMVCALNMFDETEQRGDNIDYQKIS
ELFGIPMVPTVFTNGRGVKELFHQVIAVYEGKEDETSQFRHIH
INHGHELEGGIKNIQEHLRAYPDICQRYSTRYLAIKLLEHDKDV
EELIKPLKDSDEIFKHRDIAAQRVKEETGNESETAIMDAKYGFI
Fe(2+)_transporte HGALEEADYSTGQKKDTYQTTHFIDQILTNKYFGFPIFFLILFI

r_FeoB MFTATFVIGQYPMDWIDGGVSWLGDFISSNMPDGPVKDM
LVDGIIGGVGAVIVFLPQILILYFFISYMEDSGYMARAAFIMDK
LMHKMGLHGKSFIPLIMGFGCNVPAVMATRTIESRRSRLVT
MLILPLMSCSARLPIYVMITGSFFALKYRSLAMLSLYVIGILMS
VIMSRVFSRFLVKGEDTPFVMELPPYRFPTWKAIGRHTWEK
GKQYLKKMGGIILVASIIVWALGYFPLPDKPDMGQQERQEH
SFIGQIGHAVEPVFRPQGFNWKLDVGLLAGVGAKEIVASTM
GVLYSNDDSFKDDNSFSSEGGKYVKLHKQITQDVANLHGVSY
NEAEPIATLTAFCFLLFVLLYFPCIATIAAIKGETGSWGWALFA
AGYTTLLAWVVSAIVFQVGMLFIG
MKKNLLKAVLPASLALFAVTFGSCSQDGQLTGTKEDTGERVL
DNTREIQNYLRTLPLAPMMSRASDPVPSDDGTTVPVDEGTS
KTEEKGVLNGIPGSWVKTTRRYKMTQAFDESFLFDPTSDIVY
PGCVLKGGTIANGTYAIITSHETGDVTFSINLSPANPQEARETS
ATVHNIRKSEYQEVWNKWANMQWKESPITTIESVEKINSQE
ELATKLGVAVNSPVANGSLNFGFNFNKKKNHILARLIQKYFSV
STDAPKKGNIFESIDKEALDGYQPVYISNINYGRIIYLSVESDED
34 Pneumolysin Q04IN8 EKVVDEAINFAMNQIKGVDVSVSADQSLHYRKVLANCDIRIT
VLGGGQTIQKEVLKGDIDSFQRFLNADIPMEQMSPISFSLRYA
VDNSQARVVTSNEFTVTQRDFVPEFKKVRMQLQVLGFSGTN
TGPFPNLDREAGLWGSISLSLNGQDNELVKISQSNPFFFNYRE
KKETMHPIGFGGIVTVEFDKDPNESLEDFVDHQKMTFVSDL
HSTRSIYNYNFGRTTFTHTLGTLYTKYKGDDPIFVLESNNKNV
KIHTYVKVLDMKFFN
Cluster:
MTKFIYAMSLFLLAAISIKAQPIQKTSGCLLHGSVVSSTDATAI
35 Uncharacterized G6AG77 AGATVRLYQLKKLVGGTVSDASGNFDVKCPSSGSLQLRITAV
protein GFKEVDTTLNVPTVTPLSIYMRAGKHAMDEVTVTASEKRGM

TSTTVIGQTAMEHLQPSSFADLLALLPGGMTKIPALGSANVIT
LREAGPPSSQYATSSLGTKFVIDGQAIGTDANMQYIAGSFQG
DADNSRNHVSYGVDMREIPTDNIEKVEVVRGIPSVKYGELTS
GLINITRKRSQSPLLLRLKADEYGKLVSVGKGFLLSGKWNLNV
DGGLLDARKEPRNRFETYRRLTFSARLRRKWNLGERYVLEWS
GATDYSLNIDNVKTDPEIQIHREDSYRSSYLKMGMNHRLLLR
RKALVGLQSVSLAYSASLASDRIHQTEAVALQRDYVVPLAYEG
GEYDGLFLPMQYLCDYRVEGKPFYSTLRGETEWLARTSFISH
HITAGGEFLLNKNYGRGQIFDITKPLHASTARRPRSYKDIPATD
ILSFYAEDKATMPIGKHQLTVMAGLRTTQMLNIPASYAVHGK
LFTDTRVNVQWDFPSFLGFKSFVSGGLGMMTKMPTVLDLY
PDYVYKDITEMNYWDIRPAYKRIHIRTYKLNQVNPDLRPARN
KKWEIRLGMDKGAHHFSVTYFHEDMKDGFRSTTTMRPFIYK
RYDTSVINPSALTGPPSLASLPVVTDTLLDGYGRTENGSRITKQ
GIEFQYSSPRIPVIQTRITVNGAWFRTLYENSIPLFRSAPNVVV
GTVAIADRYAGYYMSTDKYDKQIFTSNFIFDSYVDKLGLILSAT
AECFWMSNTKRPATSSTPMGYMDITGTVHPYVEADQSDPY
LRWLVLTGTAGQDMDYRERSYMLVNFKATKRFGRHLSLSFF
ADRVFYVAPDYEVNGFIVRRTFSPYFGMEIGLKI
MLIDFKKVNIYQDERLILKDIDFQATEGEFIYLIGRVGSGKSSLL
KTFYGELDIDQEDAEKAEVLGESVLDIKQKRIPALRRQMGIIFQ
Cell_division_ATP-DFQLLHDRSVAKNLKFVLQATGWKDKEKIKQRIKEVLEQVG
36 binding_protein_F P0A9R7 MIDKAAKMPSELSGGEQQRIAIARAFLNNPKIILADEPTGNLD
tsE
PETASNIVSILKDTCKNGTTVIMSTHNINLLSQFPGKVYRCME
QALVPVTNEAQTKDLEEDSTSVEPLIEPVLEEEAQAEDSKE
MFENQPKALYALALANTGERFGYYTMIAVFALFLRANFGLEP
GTAGLIYSIFLGLVYFLPLIGGIMADKFGYGKMVTIGIIVM FAG
YLFLSVPLGGGTVAFGAMLAALLLISFGTGLFKGNLQVMVGN
LYDTPELASKRDSAFSIFYMAINIGALFAPTAAVKIKEWAETSL
GYAGNDAYHFSFAVACVSLIVSMGIYYAFRSTFKHVEGGTKK
Di-TEKAAAAAVEELTPQQTKERIVALCLVFAVVIFFWMAFHQN
37 /tripeptide_transp POC2U3 GLTLTYFADEFVSPTSTGVQSMAFDVVNLVMIVFIVYSIMALF
orter QSKTTKAKGIACAVILAAIAVLAYKYMNVNGQVEVSAPIFQQ
FNPFYVVALTPISMAIFGSLAAKGKEPSAPRKIAYGMIVAGCA
YLLMVLASQGLLTPHEQKLAKAAGETVPFASANWLIGTYLVL
TFGELLLSPMGISFVSKVAPPKYKGAMMGGWFVATAIGNILV
SVGGYLWGDLSLTVVWTVFIVLCLVSASFMFLMMKRLEKVA

MKKILIFVAGLCMSLAASAQIQRPKLVVGLVVDQMRWDYLY
YYYNEYGTDGLRRLVDNGFSFENTHINYAPTVTAIGHSSVYTG
SVPAITGIAGNYFFQDDKNVYCCEDPNVKSVGSDSKEGQMS
PHRLLASTIGDELQISNDFRSKVIGVALKDRASILPAGHAADA
AYWWDTSAGHFVTSTFYTDHLPQWVIDFNEKNHTAPNFNI
Calcium-KTSTQGVTMTFKMAEAALKNENLGKGKETDMLAVSISSTDAI
38 transporting_ATPa Q47910 GHVYSTRGKENHDVYMQLDKDLAHFLKTLDEQVGKGNYLLF
se LTADHGAAHNYNYMKEHRIPAGGWDYRQSVKDLNGYLQG
KFGIAPVMAEDDYQFFLNDSLIAASGLKKQQIIDESVEYLKKD
PRYLYVFDEERISEVTMPQWIKERMINGYFRGRSGEIGVVTR
PQVFGAKDSPTYKGTQHGQPFPYDTHIPFLLYGWNVKHGAT
TQQTYIVDIAPTVCAMLHIQMPNGCIGTARNMALGN
MDRQVFQTDSRQRWNRFKWTLRVLITIAILLGVVFVAMFAL
EGSPQMPFRHDYRSVVSASEPLLKDNKRAEVYKSFRDFFKEQ
KMHSNYAKVAARQHRFVGHTDNVTQKYIKEWTDPRMGIRS
AWYVNWDKHAYISLKNNLKNLNMVLPEWYFINPKTDRIEAR
IDQRALKLMRRAHIPVLPMLTNNYNSAFRPEAIGRIMRDSTK
RMGMINELVAACKHNGFAGINLDLEELNINDNALLVTLVKDF
ARVFHANGLYVTQAVAPFNEDYDMQELAKYDDYLFLMAYD
EYNAGSQAGPVSSQRWVEKATDWAAKNVPNDKIVLGMAT
YGYNWAQGQGGTTMSFDQTMATALNAGAKVNFNDDTYN
LNFSYQDEDDGTLHQVFFPDAVTTFNIMRFGATYHLAGFGL
WRLGTEDSRIWKYYGKDLSWESAARMPIAKIMQLSGTDDV
NFVGSGEVLNVTSEPHAGRIGIVLDKDNQLIIEERYLSLPATYT
Poly-beta-1,6-N- VQRLGKCKEKQLVLTFDDGPDSRWTPKVLSILKHYKVPAAFF
acetyl-D- MVGLQIEKNIPIVKDVFNQGCTIGNHTFTHHNMIENSDRRSF

glucosamine_synt AELKLTRMLIESITGQSTILFRAPYNADADPTDHEEIWPMIIAS
hase RRNYLFVGESIDPNDWQQGVTADQIYKRVLDGVHQEYGHIIL
LHDAGGDTREPTVTALPRIIETLQREGYQFISLEKYLGMSRQTL
MPPIKKGKEYYAMQANLSLAELIYHISDFLTALFLVFLVLGFM
RLVFMYVLMIREKRAENRRNYAPIDPLTAPAVSIIVPAYNEEV
NIVRTISNLKEQDYPSLKIYLVDDGSKDNTLQRVREVFENDDK
VVIISKKNGGKASALNYGIAACSTDYIVCVDADTQLYKDAVSK
LMKHFIADKTGKLGAVAGNVKVGNQRNMLTYWQAIEYTTS
QNFDRMAYSNINAITVIPGAIGAFRKDVLEAVGGFTTDTLAE
DCDLTMSINEHGYLIENENYAVAMTEAPESLRQFIKQRIRWC
FGVMQTFWKHRASLFAPSKGGFGMWAMPNMLIFQYIIPTF
SPIADVLMLFGLFSGNASQIFIYYLIFLLVDASVSIMAYIFEHESL
WVLLWIIPQRFFYRWIMYYVLFKSYLKAIKGELQTWGVLKRT
GHVKGAQTIS

MSQINGRISQIIGPVIDVYFDTKGENPEKVLPNIYDALRVKKA
DGQDLIIEVQQQIGEDTVRCVAMDNTDGLQRGLEVVPTGSP
IVMPAGEQIKGRMMNVIGQPIDGMSALQMEGAYPIHREAP
KFEDLSTHKEMLQTGIKVIDLLEPYMKGGKIGLFGGAGVGKT
VLIMELINNIAKGHNGYSVFAGVGERTREGNDLIRDMLESGV
ATP_synthase_su IRYGEKFRKAMDEGKWDLSLVDSEELQKSQATLVYGQMNEP
40 bunit_beta,_sodiu P29707 PGARASVALSGLTVAEEFRDHGGKNGEAADIMFFIDNIFRFT
m_ion_specific QAGSEVSALLGRMPSAVGYQPTLASEMGAMQERITSTKHGS
ITSVQAVYVPADDLTDPAPATTFTHLDATTELSRKITELGIYPA
VDPLGSTSRILDPLIVGKEHYDCAQRVKQLLQKYNELQDIIAIL
GMDELSDDDKLVVNRARRVQRFLSQPFTVAEQFTGVKGVM
VPIEETIKGFNAILNGEVDDLPEQAFLNVGTIEDVKEKAKQLLE
ATKA
MNPIYKIITSILFCVLSINTMAQDLTGHVTSKADDKPIAYATVT
LKENRLYAFTDEKGNYTIKNVPKGKYTVVFSCMGYASQTVVV
MVNAGGATQNVRLAEDNLQLDEVQVVAHRKKDEITTSYTID
RKTLDNQQIMTLSDIAQLLPGGKSVNPSLMNDSKLTLRSGTL
ERGNASFGTAVEVDGIRLSNNAAMGETAGVSTRSVSASNIES
VEVVPGIASVEYGDLTNGVVKVKTRRGSSPFIVEGSINQHTRQ
IALHKGVDLGGNVGLLNFSIEHARSFLDAASPYTAYQRNVLSL
RYMNVFMKKSLPLTLEVGLNGSIGGYNSKADPDRSLDDYNK
VKDNNVGGNIHLGWLLNKRWITNVDLTAAFTYADRLSESYT
NESSNATQPYIHTLTEGYNIAEDYDRNPSANIILGPTGYWYLR
GFNDSKPLNYSLKMKANWSKAFGKFRNRLLVGGEWTSSMN
Cluster:
RGRGTYYADMRYAPSWREYRYDALPSLNNIAIYAEDKLSMD
41 Uncharacterized G6AGX5 VNERQNAELTAGIREDITSIPGSEYGSVGSFSPRMNARYVFRF
protein GQNSWLNSMTLHAGWGRSVKIPSFQVLYPSPSYRDMLAFA
STSDADNRSYYAYYTYPSMARYNANLKWQRADQWDLGVE
WRTKIADVSLSFFRSKVSNPYMATDVYTPFTYKYTSPAMLQR
SGIAVADRRFSIDPQTGIVTVSDASGVKSPVTLGYEERNTYVT
NTRYVNADALQRYGLEWIVDFKQIKTLRTQVRLDGKYYHYKA
QDETLFADVPVGLNTRQSDGRLYQYVGYYRGGAATTTNYTA
NASASNGSVSGQVDLNATITTHIPKIRLIVALRLESSLYAFSRAT
SSRGYVVSSGNEYFGVPYDDKTENQTVIVYPEYYSTWDAPDV
LIPFAEKLRWAETNDRGLFNDLAQLVVRTNYPYTLNPNRLSA
YWSANLSVTKEIGRHVSVSFYANNFFNTLSQVHSTQTGLETSL
FGSGYVPSFYYGLSLRLKI
[114] In some embodiments, the Prevotella bacteria is a strain of Prevotella bacteria free or substantially free of one or more (e.g., 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more) proteins listed in Table 2 and/or one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more) genes encoding proteins listed in Table 2. In some embodiments, Prevotella bacteria is free of all of the proteins listed in Table 2 and/or all of the genes encoding the proteins listed in Table 2.
Table 2: Other Prevotella proteins Seq. Name Uniprot ID
Amino Acid Sequence ID. No.
MERIDISVLMAVYKKDNPAFLRESLESIFSQTVEAAEVVLLED
GPLTDALYDVIKSYEAIYSTLKVVSYPENRGLGKTLNDGLLLCK
UDP-Gal:alpha-D-YNLVARMDADDICKPNRLEMEYNWLKSHEDYDVIGSWVDE
GIcNAc-diphosphoundeca VLAVGGYLTEYFPEDYFLWLRMLNNGSKFYNIQESLLWFRYS
prenol EETVAKRGGWAYACDEVRILVRMLKMGYIPFHVFCQSVVIRF
TTRVMPLPIRQRLYNLIRKT
MSQINGRISQIIGPVIDVYFDTKGENPEKVLPKIHDALRVKRA
NGQDLIIEVQQHIGEDTVRCVAMDNTDGLQRNLEVVPTGSP
IVMPAGDQIKGRMMNVIGQPIDGMEALSMEGAYPIHREAP
KFEDLSTHKEMLQTGIKVIDLLEPYMKGGKIGLFGGAGVGKT
VLIMELINNIAKGHNGYSVFAGVGERTREGNDLIRDMLESGV
IRYGEKFRKAMDEGKWDLSLVDQEELQKSQATLVYGQMNE
ATP_synthase_su bunit beta _ TQAGSEVSALLGRMPSAVGYQPTLASEMGTMQERITSTKHG
SITSVQAVYVPADDLTDPAPATTFTHLDATTELSRKITELGIYP
AVDPLGSTSRILDPLIVGKDHYECAQRVKQLLQHYNELQDIIAI
LGMDELSDEDKLVVNRARRVQRFLSQPFTVAEQFTGVKGV
MVPIEETIKGFNAILNGEVDDLPEQAFLNVGTIEDVKEKAKRL
LEATK
MPIGNGQKYQLTIINHTEIIMLIDYKKVNIYQDERLILKDVDFQ
AETGEFIYLIGRVGSGKSSLLKTIYGELDIDSEDAEKAVVLDES
Cell_division_ATP- MPNIKRSRIPALRKQMGIIFQDFQLLHDRSVAKNLKFVLQAT
44 binding_protein_F 005779 GWTSKQKIERRIEEVLAQVGMTDKKNKMPSELSGGEQQRIA
tsE IARALLNTPKIIIADEPTGNLDPETAANIVSILKDSCQAGTTVIM
STHNINLIDQFPGKVYRCHEGELHQLTDKKEVSELAEETAPVE
TIDEPEQND

MKRNILLFICLATSILLLFGLNLTTGSVQIPFADILDILCGRFIGKE
SWEYIILENRLPQTLTAILCGASLSVCGLMLQTAFRNPLAGPD
VFGISSGAGLGVALVMLLLGGTVSTSIFTVSGFLAILTAAFVGA
Hemin_transport_ IAVTALILFLSTLVRNSVLLLIVGIMVGYVSSSAVSLLNFFASEEG
45 system_permease Q56992 VKSYMVWGMGNFGAVSMNHIPLFSILCLIGIIASFLLVKPLNIL
_protein_HmuU
LLGPQYAESLGISTRQIRNILLVVVGLLTAITTAFCGPISFIGLAIP
HIARLLFRTENHQILLPGIVLSGAAIALLCNFICYLPGESGIIPLN
AVTPLIGAPIIIYVIIQRR
MKKYYPWVLVALLWFVALLNYMDRQMLSTMQEAMKVDIA
ELNHAEAFGALMAVFLWIYGIVSPFAGIIADRVNRKWLVVGS
IFVWSAVTYLMGYAESFDQLYWLRAFMGISEALYIPAALSLIA
DWHEGKSRSLAIGIHMTGLYVGQAVGGFGATLAAMFSWHA
Hexuronate trans AFHWFGIIGIVYSLVLLLFLKENPKHGQKSVLQGETKPSKNPFR
46 _ porter GLSIVFSTWAFWVILFYFAVPSLPGWATKNWLPTLFANSLDIP
MSSAGPMSTITIAVSSFIGVIMGGVISDRWVQRNLRGRVYTS
AIGLGLTVPALMLLGFGHSLVSVVGAGLCFGIGYGMFDANN
MPILCQFISSKYRSTAYGIMNMTGVFAGAAVTQVLGKWTDG
GNLGNGFAILGGIVVLALVLQLSCLKPTTDNME
MVTKKTTTKKAPVKKTSAKTTKVKEPSHIGLVKNDAYLAPYED
AIRGRHEHALWKMNQLTQNGKLTLSDFANGHNYYGLHQTA
DGWVFREWAPNATEIYLVGDFNGWNEQEAYQCHRIEGTG
NWELTLPHDAMQHGQYYKMRVHWEGGEGERIPAWTQRV
VQDEASKIFSAQVWAPAEPYVWEKKTFKPQTSPLLIYECHIG
MAQDEEKVGTYNEFREKVLPRIIKDGYNAIQIMAIQEHPYYG
SFGYHVSSFFAASSRFGTPEELKALIDEAHKNGIAVIMDIVHSH
1,4-alpha- AVKNEVEGLGNLAGDPNQYFYPGERHEHPAWDSLCFDYGK
47 glucan_branching P9WN45 DEVLHFLLSNCKYWLEEYHFDGFRFDGVTSMLYYSHGLGEAF
_enzyme_GIgB CNYADYFNGHQDDNAICYLTLANCLIHEVNKNAVTIAEEVSG
MPGLAAKFKDGGYGFDYRMAMNIPDYWIKTIKELPDEAWK
PSSIFWEIKNRRSDEKTISYCESHDQALVGDKTIIFRLVDADMY
WHFRKGDETEMTHRGIALHKMIRLATIAAINGGYLNFMGNE
FGHPEWIDFPREGNGWSHKYARRQWNLVDNEELCYHLLGD
FDRKMLEVITSEKKFNETPIQEIWHNDGDQILAFSRGELVFVF
NFSPSHSYSDYGFLVPEGSYNVVLNTDAREFGGFGFADDTVE
HFTNSDPLYEKDHKGWLKLYIPARSAVVLRKK
MKIDIERIKYFLTVGMFMKTEHSSKRRNMLIRQFQKFYLTVKF

Cluster: YihY D9RW24 FFVRDHAASTAQLSFSTIMAIVPIASMIFAIANGFGFGQFLEK
family protein QFREMLSAQPEAATWLLKLTQSYLVHAKTGLFIGIGLMIMLY
SVFSLIRTVETTFDNIWQVKDSRPISRIVIDYTALMFLVPISIIILS

GLSIYFYSFVENLNGLRFLGTIASFSLRYLVPWAILTLMFIVLYV
FMPNAKVKITKTVAPAMIASIAMLCLQAVYIHGQIFLTSYNAI
YGSFAALPLFMLWILASWYICLFCAELCYFNQNLEYYECLIDTE
DICHNDLLILCATVLSHICQRFANDQKPQTALQIKTETHIPIRV
MTDILYRLKEVNLISENFSPTSDEVTYTPTHDTNNITVGEMIA
RLESTPASDFALLGFSPKKAWNHDIYDRVGSIREIYLNELKSINI
KELISYSEN
MMKRPSIARVVKVIICLLTPILLSFSGIGDNDIDKKKSTSKEVDD
TLRIVITGDLLLDRGVRQKIDMAGVDALFSPTIDSLFHSSNYVI
ANLECPVTKIRERVFKRFIFRGEPEWLPTLRRHGITHLNLANN
Capsule_biosynth HSIDQGRNGLLDTQEQIKKAGMIPIGAGKNMEEAAEPVLIST
49 esis_ A protein_Cap P19579 SPRHVWVISSLRLPLENFLYLPQKPCVSQESIDSLIMRVKRLRA
TDKNCYILLILHWGWEHHFRATPQQREDAHKLIDAGADAIV
GHHSHTLQTIETYRGKPIYYGIGNFIFDQRKPMNSRACLVELSI
TAEKCKAKALPIEIKNCTPYLSK
MILLSFDTEEFDVPREHGVDFSLEEGMKVSIEGTNRILDILKAN
NVCATFFCTGNFAELAPEVMERIKNEGHEVACHGVDHWQP
KPEDVFRSKEIIERVTGVKVAGYRQPRMFPVSDEDIEKAGYLY
Peptidoglycan_de acetylase PLFWLSMHNFPEWFYLRLVRQVLRHDGYFVTYFHPWEFYDL
KSHPEFKMPFIIKNHSGHELEQRLDRFIKAMKADKQEFITYVD
FVNRQKK
MAKNISFTIKYWKQNGPQDQGHFDTHEMKNIPDDTSFLEM
LDILNEELIAAGDEPFVFDHDCREGICGMCSLYINGTPHGKTE
Fumarate_reducta RGATTCQLYMRRFNDGDVITVEPWRSAGFPVIKDCMVDRT
51 se_iron- P0AC47 AFDKIIQAGGYTTIRTGQAQDANAILISKDNADEAMDCATCI
sulfur_subunit GCGACVAACKNGSAMLFVSSKVSQLALLPQGKPEAAKRAKA
MVAKMDEVGFGNCTNTRACEAVCPKNEKIANIARLNREFIK
AKFAD
MSENKLSTNEQAQTADAPVKASYTEYKVIPSQGYCMIVKCRK
GDQTVVLKTLKEEYRERVLLRNALKREFKQCQRLNHSGIVRY
Serine/threonine-QGLVEVDGYGLCIEEEYVEGRTLQAYLKENHTDDEKIAIINQIA
52 protein_kinase_Pk P9WI71 DALRYAHQQGVIHRNLKPSNVLVTTQGDYVKLIDFSVLSPED
nH VKPTAETTRFMAPEMKDETLTADATADIYSLGTIMKVMGLTL
AYSEVIKRCCAFKRSDRYSNVDELLADLNNEGSSFSMPKIGKG
TVVLGLIIAVVIGIGALLYNYGGALIDQVGKIDVSSVFSSDAETA
PEDTVKVNTAEQSDSLSTEAEAPAIGKLAFMNRMKPALYKDL

DNIFEKNSADKAKLTKAIKTYYRGLIQANDTLDNEQRAEVDRV
FGDYVKQKKAALN
MRKYICLLLFYLFTFLPLSAQQGNDSPLRKLQLAEMAIKNFYV
DSVN EQKLVE DG I RG M LE KLDP HSTYTDAKETKAM NE PLQG
DFEGIGVQFNMIEDTLVVIQPVVNGPSQKVGILAGDRIVSVN
DSTIAGVKMARIDIMKMLRGKKGTKVKLGVVRRGVKGVLTF
VVTRAKI PVHTI NASYM I RP NVGYI RI ESFG M KTH DE F MSAV
Carboxy- DSLKKKGMKTLLLDLQDNGGGYLQSAVQISNEFLKNNDMIV
53 terminal_processi 034666 YTEGRRARRQNFKAIGNGRLQDVKVYVLVNELSASAAEIVTG
ng_protease_CtpA AIQDNDRGTVVGRRTFGKGLVQRPFDLPDGSMIRLTIAHYYT
PSGRCIQKPYTKGDLKDYEMDIEKRFKHGELTNPDSIQFSDSL
KYYTI R KHRVVYGGGG I MPDNFVPLDTTKFTRYHRMLAAKSI I
INAYLKYADANRQALKAQYSSFDAFNKGYVVPQSLLDEIVAE
GKKEKIEPKDAAELKATLPNIALQI KALTARD IWD M NEYF RV
WNTQSDIVNKAVALATGK
MKLTEQRSSMLHGVLLITLFACAAFYIGDMGWVKALSLSPM
VVGIILGMLYANSLRNNLPDTWVPGIAFCGKRVLRFGIILYGF
RLTFQDVVAVGFPAIIVDAIIVSGTILLGVLVGRLLKMDRSIALL
Cluster: TACGSGICGAAAVLGVDGAIRPKPYKTAVAVATVVIFGTLSM
54 Uncharacterized D9R RG3 FLYPI LYRAG I F DLSPDAMG I
FAGSTI H EVAHVVGAG NAMGA
protein AVSNSAIIVKMIRVMMLVPVLLVIAFFVAKNVAERDDEAGGS
RKI NI PWFAI LFLVVIG F NSLN LLPKE LVDF I NTLDTF LLTMAMS
ALGAETSIDKFKKAGFKPFLLAAILWCWLIGGGYCLAKYLVPV
LGVAC
MNKQFLLAALWLSPLGLYAHKANGIGAVTWKNEAPKERMI
RGIDEDKTHQRFTLSGYVKDRNGEPLINATIYDLTTRQGTMT
NAYG H FSLTLG EGQH El RCSYVGYKTLI ETI DLSANQN HDI I LQ
NEAQLDEVVVTTDLNSPLLKTQTGKLSLSQKDIKTEYALLSSPD
VIKTLQRTSGVADGMELASGLYVHGGNGDENLFLLDGTPLY
HTNHSLGLFSSFNADVVKNVDFYKSGFPARYGGRLSSVIDVR
Cluster: Cna TADGDLYKTHGSYRIGLLDGAFHIGGPIRKGKTSYNFGLRRSW
55 protein B-type X6Q2J4 MDLLTRPAFAIMNHKSDNEDKLSMSYFFHDLNFKLTNIFNER
domain protein SRMSLSVYSGEDRLDAKDEWHSNNSSGYNDVDIYVNRFHW
GNFNAALDWNYQFSPKLFANFTAVYTHNRSTVSSSDEWRFT
RPGEKEQLTLTSHGYRSSIDDIGYRAAFDFRPSPRHHIRFGQD
YTYHRFQPQTYNRFDNYQTNSEAKADTIATHSYNKNVAHQL
TFYAEDEMTLNEKWSLNGGVNADVFHISGKTFATLSPRLSM
KFQPTERLSLKASYTLMSQFVHKIANSFLDLPTDYWVPTTARL
HPMRSWQVAAGAYMKPNKHWLLSLEAYYKRSSHILQYSSW

AGLEPPAANWDYMVMEGDGRSYGVELDADYNVSNLTLHG
SYTLSWTQKKFDDFYDGWYYDKFDNRHKLTLTGRWNITKKI
AAFAAWTFRTGNRMTIPTQYIGLPDVPAQEQGGLTFNSSDD
NTLNFAYEKPNNVILPAYHRLDIGFDFHHTTKKGHERIWNLSF
YNAYCHLNSLWVRVKIDSNNQMKIRNIAFIPVIPSFSYTFKF
MSKQVFQTDSRQRWSYFKWTLRVILTILSLLGIVFLAMFALEG
SPQMPFRHDYRNAVTAASPYTKDNKTAKLYKSFRDFFKEKK
MHNNYAKATIKKQRFIGKADSVTQKYFREWDDPRIGVRSA
WYVNWDKHAYISLKNNIKHLNMVLPEWFFINPKTDKVEYRI
DKQALRLMRRTGIPVLPMLTNNYNSDFHPEAIGRIMRDEKK
RMALINEMVRTCRHYGFAGINLDLEELNIQDNDLLVELLKDFS
RVFHANGLYVTQAVAPFNEDYNMQELAKYNDYLFLMAYDE
HNIESQPGAVSSQRWVEKATDWAAKNVPNDKIVLGMATYG
YDWANGEGGTTVSFDQTMAIAQDADAKVKFDDDTYNVNF
SYQNTDDGKIHHVFFTDAATTFNIMRFGAEYHLAGYGLWRL
GTEDKRIWRFYGKDMSWENVARMSVAKLMQLNGTDDVNF
VGSGEVLEVTTEPHPGDISIRIDKDNRLISEEYYRALPSTYTIQR
Poly-beta-1,6-N- LGKCKDKQLVITFDDGPDSRWTPTVLSTLKKYNVPAAFFMVG
acetyl-D- LQMEKNLPLVKQVYEDGHTIGNHTFTHHNMIENSDRRSYAE

glucosamine_synt LKLTRMLIESVTGHSTILFRAPYNADADPTEHEEIWPMIVASR
hase RNYLFVGESIDPNDWEPNVTSDQIYQRVIDGVHHEDGHIILL
HDAGGSSRKPTLDALPRIIETLQHEGYQFISLEQYLGMGKQTL
MPEINKGKAYYAMQTNLWLAEMIYHVSDFLTALFLVFLALG
MMRLIFMYVLMIREKRAENRRNYAPIDAATAPAVSIIVPGYN
EEVNIVRTITTLKQQDYPNLHIYFVDDGSKDHTLERVHEAFDN
DDTVTILAKKNGGKASALNYGIAACRSEYVVCIDADTQLKND
AVSRLMKHFIADTEKRVGAVAGNVKVGNQRNMLTYWQAIE
YTSSQNFDRMAYSNINAITVVPGAIGAFRKEVIEAVGGFTTDT
LAEDCDLTMSINEHGYIIENENYAVALTEAPETLRQFVKQRIR
WCFGVMQAFWKHRSSLFAPSKKGFGLWAMPNMLIFQYIIP
TFSPLADVLMLIGLFTGNALQIFFYYLIFLVIDASVSIMAYIFEGE
RLWVLLWVIPQRFFYRWIMYYVLFKSYLKAIKGELQTWGVLK
RTGHVKG
MAKKRNKARSRHSLQVVTLCISTAMVLMLIGIVVLTGFTSRN
Cell_division_prot LSSYVKENLTITMILQPDMNTEESAALCERIRTLHYINSLNFISK
57 ein FtsX 034876 EQALKDGTKELGANPAEFAGENPFTGEIEVQLKANYANNDSI
_ RNIVQQLRTYRGVSDITYPQSLVESVNQTLGKISLVLLVIAVLLT
IISFSLINNTIRLSIYAHRFSIHTMKLVGGSWSFIRAPFLRRAVLE

GLVSALLAIAVLGIGICLLYEKEPEITKLLSWDALIITAIVMLAFG
VIIATFCAWLSVNKFLRMKAGDLYKI
MKNIYFLSDAHLGSLAIDHRRTHERRLVRFLDSIKHKAAAVYLL
GDMFDFWNEYKYVVPKGFTRFLGKISELTDMGVEVHFFTGN
UDP-2,3- HDLWTYGYLEKECGVILHRKPITTEIYDKVFYLAHGDGLGDPD
58 diacylglucosamine P44046 PMFRFLRKVFHNRFCQRLLNFFHPWWGMQLGLNWAKRSR
_hydrolase LKRKDGKEVPYLGEDKEYLVQYTKEYMSTHKDIDYYIYGHRHI
ELDLTLSRKARLLILGDWIWQFTYAVFDGEHMFLEEYVEGESK
P
MVGLDVLCYFIHAKGREKECYFERIIYQITCHSRTKCYLCNIMK
YSIIVPVFNRPDEVEELLESLLSQEEKDFEVVIVEDGSQIPCKEV
CDKYADKLDLHYYSKENSGPGQSRNYGAERAKGEYLLILDSD
Poly-beta-1,6-N- VVLPKGYICAVSEELKREPADAFGGPDCAHESFTDTQKAISYS
acetyl-D- MTSFFTTGGIRGGKKKLDKFYPRSFNMGIRRDVYQELGGFSK

glucosamine_synt MRFGEDIDFSIRIFKAGKRCRLFPEAWVWHKRRTDFRKFWK
hase QVYNSGIARINLYKKYPESLKLVHLLPMVFTVGTALLVLMILFG
LFLQLFPIINVFGSVFIMMGLMPLVLYSVIICVDSTMQNNSLNI
GLLSIEAAFIQLTGYGCGFISAWWKRCVCGMDEFAAYEKNFY
K
MKIEKVHAREIMDSRGNPTVEVEVTLENGVMGRASVPSGAS
TGENEALELRDGDKNRFLGKGVLKAVENVNNLIAPALKGDCV
LNQRAIDYKMLELDGTPTKSKLGANAILGVSLAVAQAAAKAL
NIPLYRYIGGANTYVLPVPMMNIINGGAHSDAPIAFQEFMIR
PVGAPSEKEGIRMGAEVFHALAKLLKKRGLSTAVGDEGGFAP
60 Enolase Q8DTS9 KFDGIEDALDSIIQAIKDAGYEPGKDVKIAMDCAASEFAVCED
GKWFYDYRQLKNGMPKDPNGKKLSADEQIAYLEHLITKYPID
SIEDGLDENDWENWVKLTSAIGDRCQLVGDDLFVTNVKFLE
KGIKMGAANSILIKVNQIGSLTETLEAIEMAHRHGYTTVTSHR
SGETEDTTIADIAVATNSGQIKTGSMSRTDRMAKYNQURIEE
ELGACAKYGYAKLK
MKKLFTIAMLLGVTLGIHAQEVYSLQKCRELALQNNRQLKVS
RMTVDVAENTRKAAKTKYLPRVDALAGYQHFSREISLLSDDQ
Outer_membrane KNAFSNLGTNTFGQLGGQIGQNLTSLAQQGILSPQMAQQL
61 _efflux_protein_B Q8G0Y6 GQLFSNVATPLTQVGNNIGQSINDAFRSNTKNVYAGGIVVN
epC QPIYMGGAIKAANDMAAIGEQVAQNNISLKRQLVLYGVDN
AYWLAISLKKKEALAIRYRDLAQKLNEDVKKMIREGVATRAD
GLKVEVAVNTADMQIARIQSGVSLAKMALCELCGLELNGDIP
LSDEGDADLPPTPSTQFDNYTVSSSDTTGLNEARPELRLLQNA

VDLSIQNTKLIRSLYMPHVLLTAGYSVSNPNLFNGFQKRFTDL
WNIGITVQVPVWNWGENKYKVRASKTATTIAQLEMDDVRK
KIDLEIEQNRLRLKDANKQLATSQKNMAAAEENLRCANVGFK
EGVMTVTEVMAAQTAWQTSRMAIIDAEISVKLAQTGLQKA
LGGL
MKRTFVTKMVKPIEENSLFFMFMLLVGAFTNVSHRNVFGYIE
LIADVYIICFLLSLCQRTIRQGLVIMLSSVIYVVAIIDTCCKTLFDT
PITPTMLLLAQETTGREATEFFLQYLNLKLFFSAADIILFLAFCHI
VMAVKKMKFSTSYLKQPFVAFVLMFTIFVGMALSIYDKVQLY
TVKNLSGLEVAVTNGFAHLYHPVERIVYGLYSNHLIAKQVDG
VIMANQQIKVDSCSFTSPTIVLVIGESANRHHSQLYGYPLPTT
Phosphoethanola PYQLAMKNGKDSLAVFTNVVSPWNLTSKVFKQIFSLQSVDE
62 mine transferase Q7CPCO
_ KGDWSKYVLFPAVFKKAGYHVSFLSNQFPYGINYTPDWTNN
_CptA
LVGGFFLNHPQLNKQMFDYRNVTIHNYDEDLLNDYKEIISYK
KPQLIIFHLLGQHFQYSLRCKSNMKKFGIKDYKRMDLTDKEK
QTIADYDNATLYNDFVLNKIVEQFRNKDAIIVYLSDHGEDCYG
KDVNMAGRLTEVEQINLKKYHEEFEIPFWIWCSPIYKQRHRKI
FTETLMARNNKFMTDDLPHLLLYLAGIKTKDYCEERNVISPSF
NNNRRRLVLKTIDYDKALYQ
MFKNHPKGLLQAAFSNMGERFGYVIMNAVLALFLCSKFGLS
DETSGLIASLFLAAIYVMSLVGGVIADRTQNYQRTIESGLVVM
ALGYVALSIPVLATPENNSYLLAFTIFALVLIAVGNGLFKGNLQ
AIVGQMYDDFETEAAKVSPERLKWAQGQRDAGFQIFYVFIN
LGALAAPFIAPVLRSWWLGRNGLTYDAALPQLCHKYINGTIG
Dipeptide_and_tri DNLGNLQELATKVGGNSADLASFCPHYLDVFNTGVHYSFIAS
63 peptide_permeas P36837 VVTMLISLIIFMSSKKLFPMPGKKEQIVNVEYTDEEKASMAKEI
e_B KQRMYALFAVLGISVFFWFSFHQNGQSLSFFARDFVNTDSV
APEIWQAVNPFFVISLTPLIMWVFAYFTKKGKPISTPRKIAYG
MGIAGFAYLFLMGFSLVHNYPSAEQFTSLEPAVRATMKAGP
MILILTYFFLTVAELFISPLGLSFVSKVAPKNLQGLCQGLWLGA
TAVGNGFLWIGPLMYNKWSIWTCWLVFAIVCFISMVVMFG
MVKWLERVTKS
MQKKIKIGLLPRVIIAILLGLFLGYYLPDPAVRVFLTFNSIFSQFL
GFMIPLIIIGLVTPAIAGIGKGAGKLLLATVAIAYVDTIVAGGLS

64 dicarboxylate_tra Q9I4F5 MSSLVFSFIAGLGIAYGGLRTMENLFNEFKTVIEKVIEKAIIPLL
nsport_protein_2 PLYIFGVFLSMTHNGQARQVLLVFSQIIIVILVLHVLILIYEFCIA
GAIVKHNPFRLLWNMLPAYLTALGTSSSAATIPVTLKQTVKN
GVSEEVAGFVVPLCATIHLSGSAMKITACALTICMLTDLPHDP

GLFIYFILMLAIIMVAAPGVPGGAIMAALAPLSSILGFNEEAQA
LMIALYIAMDSFGTACNVTGDGAIALAVNKFFGKKKETSILS
MISVYSIKPQFQRVLTPILELLHRAKVTANQITLWACVLSLVIGI
LFWFAGDVGTWLYLCLPVGLLIRMALNALDGMMARRYNQI
Inner membrane 65 _ TRKGELLNEVGDVVSDTIIYFPLLKYHPESLYFIVAFIALSIINEYA
_protein_YnbA
GVMGKVLSAERRYDGPMGKSDRAFVLGLYGVVCLFGINLSG
YSVYIFGVIDLLLVLSTWIRIKKTLKVTRNSQTPE
MKLSTILLSIMLGLSSSTMAQQKDVTIKLIETTDVHGSFFPYDF
ITRKPKSGSMARVYTLVEELRKKDGKDNVYLLDNGDILQGQPI
SYYYNYVAPEKTNIAASVLNYMGYDVATVGNHDIETGHKVY
DKWFKELKFPILGANIIDTKTNKPYILPYYTIKKKNGIKVCVIGM
LTPAIPNWLKESIWSGLRFEEMVSCAKRTMAEVKTQEKPDVI
VGLFHSGWDGGIKTPEYDEDASKKVAKEVPGFDIVFFGHDH
2',3'-cyclic- TPHSSIEKNIVGKDVICLDPANNAQRVAIATLTLRPKTVKGKR

nucleotide QYTVTKATGELVDVKELKADDAFIQHFQPEIDAVKAWSDQVI
GRFENTIYSKDSYFGNSAFNDLILNLELEITKADIAFNAPLLFNA
SIKAGPITVADMFNLYKYENNLCTMRLTGKEIRKHLEMSYDL
WCNTMKSPEDHLLLLSSTQNDAQRLGFKNFSFNFDSAAGID
YEVDVTKPDGQKVRILRMSNGEPFDENKWYTVAVNSYRAN
GGGELLTKGAGIPRDSLKSRIIWESPKDQRHYLMEEIKKAGV
MNPQPNHNWKFIPETWTVPAAARDRKLLFGE
MKLSELKTGETGVIVKVSGHGGFRKRIIEMGFIKGKTVEVLLN
APLQDPVKYKIMGYEVSLRHSEADQIEVLSDVKTHSVGNEEE
QEDNQLEMDSTTYDSTDKELTPEKQSDAVRRKNHTINVALV
GNPNCGKTSLFNFASGAHERVGNYSGVTVDAKVGRAEFDGY
VFNLVDLPGTYSLSAYSPEELYVRKQLVDKTPDVVINVIDSSNL
ERNLYLTTQLIDMHIRMVCALNMFDETEQRGDHIDAQKLSEL
FGVPMIPTVFTNGRGVKELFRQIIAVYEGKEDESLQFRHIHIN
HGHEIENGIKEMQEHLKKYPELCHRYSTRYLAIKLLEHDKDVE

Fe(2+)_transporte P33650 QLVSPLGDSIEIFNHRDTAAARVKEETGNDSETAIMDAKYGFI
r_FeoB NGALKEANFSTGDKKDTYQTTHVIDHVLTNKYFGFPIFFLVLL
VMFTATFVIGQYPMDWIEAGVGWLGEFISKNMPAGPVKD
MIVDGIIGGVGAVIVFLPQILILYFFISYMEDCGYMSRAAFIMD
RLMHKMGLHGKSFIPLIMGFGCNVPAVMATRTIESRRSRLIT
MLILPLMSCSARLPIYVMITGSFFALKYRSLAMLSLYIIGVLMA
VAMSRLFSAFVVKGEDTPFVMELPPYRFPTWKAIGRHTWEK
GKQYLKKMGGIILVASIIVWALGYFPLPDDPNMDNQARQEQ
SYIGRIGKAVEPVFRPQGFNWKLDVGLLSGMGAKEIVASTM
GVLYSNDGSFSDDNGYSSETGKYSKLHNLITKDVATMHHISY

EEAEPIATLTAFSFLLFVLLYFPCVATIAAIKGETGSWGWALFA
AGYTTALAWIVSAVVFQVGMLFM
MESFIIEGGHQLSGTIAPQGAKNEALEVICATLLTSEEVIIRNVP
DILDVNNLIKLLQDIGVKVKKLAPNEFSFQADEVNLDYLESSDF
VKKCSSLRGSVLMIGPLLGRFGKATIAKPGGDKIGRRRLDTHF
LGFKNLGAHFGRVEDRDVYEIQADKLVGTYMLLDEASITGTA
NIIMAAVLAEGTTTIYNAACEPYIQQLCKMLNAMGAKISGIAS
UDP-N-NLITIEGVKELHSADHRILPDMIEVGSFIGIAAMIGDGVRIKDV
acetylglucosamine SVPNLGLILDTFHRLGVQIIVDNDDLIIPRQDHYVIDSFIDGTIM
TISDAPWPGLTPDLISVLLVVATQAQGSVLFHQKMFESRLFFV
DKLIDMGAQIILCDPHRAVVVGHDNAKKLRAGRMSSPDIRA
GIALLIAALTAQGTSRIDNIVQIDRGYENIEGRLNALGAKIQRA
EVC
MNIAVIFAGGSGLRMHTKSRPKQFLDLNGKPIIIYTLELFDNH
PNIDAIVVACIESWIPFLEKQLRKFEINKVVKIIPGGKSGQESIY
Ribito1-5-KGLCAAEEYAQSKGVSNEETTVLIHDGVRPLITEETITDNIKKV
69 phosphate_cytidyl Q8RKI9 EEVGSCITCIPATETLIVKQADDALEIPSRADSFIARAPQSFRLI
yltransferase DIITAHRRSLAEGKADFIDSCTMMSHYGYKLGTIIGPMENIKIT
TPTDFFVLRAMVKVHEDQQIFGL

[115] In some embodiments, the Prevotella bacteria are from a strain of Prevotella bacteria comprising one or more of the proteins listed in Table 1 and that is free or substantially free of one or more proteins listed in Table 2. In some embodiments, the Prevotella bacteria are from a strain of Prevotella bacteria that comprises all of the proteins listed in Table 1 and/or all of the genes encoding the proteins listed in Table 1 and that is free of all of the proteins listed in Table 2 and/or all of the genes encoding the proteins listed in Table 2.
Pharmaceutical Compositions

[116] In certain embodiments, provided herein are pharmaceutical compositions comprising Prevotella bacteria (e.g., a Prevotella bacteria described herein), e.g., for use in methods of treating or preventing a TH2-mediated condition (such as atopic dermatitis, asthma, and/or an allergy). In some embodiments, the Prevotella bacteria composition comprises Prevotella bacteria and/or a combination of bacteria strains described herein and a pharmaceutically acceptable carrier. In some embodiments, the Prevotella bacteria composition comprises a single Prevotella bacteria strain described herein and a pharmaceutically acceptable carrier.

[117] In some embodiments, the pharmaceutical compositions comprise Prevotella bacteria and one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) of bacteria strains or species, e.g., in addition to Prevotella. In some embodiments, the pharmaceutical compositions comprise Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises lyophilized Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises gamma irradiated Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises live Prevotella bacteria.

[118] In some embodiments, to quantify the numbers of Prevotella bacteria present in a bacterial sample, electron microscopy (e.g., EM of ultrathin frozen sections) can be used to visualize the bacteria and count their relative numbers. Alternatively, nanoparticle tracking analysis (NTA), Coulter counting, or dynamic light scattering (DLS) or a combination of these techniques can be used. NTA and the Coulter counter count particles and show their sizes. DLS
gives the size distribution of particles, but not the concentration. Bacteria frequently have diameters of 1-2 um (microns). The full range is 0.2-20 um. Combined results from Coulter counting and NTA can reveal the numbers of bacteria in a given sample. Coulter counting reveals the numbers of particles with diameters of 0.7-10 um. For most bacterial samples, the Coulter counter alone can reveal the number of bacteria. For NTA, a Nanosight instrument can be obtained from Malvern Panalytical. For example, the NS300 can visualize and measure particles in suspension in the size range 10-2000nm. NTA allows for counting of the numbers of particles that are, for example, 50-1000 nm in diameter. DLS reveals the distribution of particles of different diameters within an approximate range of 1 nm ¨ 3 um.

[119] In some embodiments, the Prevotella bacteria may be quantified based on particle count. For example, total particle content of a Prevotella bacteria can be measured using NTA.

[120] In some embodiments, the Prevotella bacteria may be quantified based on total cell count (TCC) (e.g., determined by Coulter counter).

[121] In some embodiments, the Prevotella bacteria may be quantified using a plate count assay (e.g., by creating serial dilutions of the bacteria, allowing them to grow on a suitable medium, and then counting the number of colonies).

[122] In some embodiments, the Prevotella bacteria may be quantified based on the amount of protein, lipid, or carbohydrate. For example, total protein content of a Prevotella bacteria preparation can be measured using the Bradford assay or the BCA
assay.

[123] In some embodiments, the Prevotella bacteria are isolated away from one or more other bacterial components, e.g., of the source culture. In some embodiments, the pharmaceutical composition further comprises other bacterial components or strains.

[124] In certain aspects, provided are pharmaceutical compositions for administration to a subject (e.g., human subject). In some embodiments, the pharmaceutical compositions are combined with additional active and/or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose format.

[125] In some embodiments, the pharmaceutical composition comprises at least one carbohydrate.

[126] In some embodiments, the pharmaceutical composition comprises at least one lipid. In some embodiments the lipid comprises at least one fatty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1), margaric acid (17:0), heptadecenoic acid (17:1), stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20:1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EPA), docosanoic acid (22:0), docosenoic acid (22:1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and tetracosanoic acid (24:0).

[127] In some embodiments, the pharmaceutical composition comprises at least one supplemental mineral or mineral source. Examples of minerals include, without limitation:
chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.

[128] In some embodiments, the pharmaceutical composition comprises at least one supplemental vitamin. The at least one vitamin can be fat-soluble or water-soluble vitamins.
Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin. Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of the vitamin, and metabolites of the vitamin.

[129] In some embodiments, the pharmaceutical composition comprises an excipient.
Non-limiting examples of suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.

[130] In some embodiments, the excipient is a buffering agent. Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.

[131] In some embodiments, the excipient comprises a preservative. Non-limiting examples of suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol.

[132] In some embodiments, the pharmaceutical composition comprises a binder as an excipient. Non-limiting examples of suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof.

[133] In some embodiments, the pharmaceutical composition comprises a lubricant as an excipient. Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

[134] In some embodiments, the pharmaceutical composition comprises a dispersion enhancer as an excipient. Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high EILB
emulsifier surfactants.

[135] In some embodiments, the pharmaceutical composition comprises a disintegrant as an excipient. In some embodiments the disintegrant is a non-effervescent disintegrant. Non-limiting examples of suitable non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth. In some embodiments the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.

[136] In some embodiments, the pharmaceutical composition is a food product (e.g., a food or beverage) such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed. Specific examples of the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers;
carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, and Chinese soups; soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products, including biscuits, cookies, and the like, candies, chewing gums, gummies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soy-bean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, tablets, capsules, liquids, pastes, and jellies.

[137] In some embodiments, the pharmaceutical composition is a food product for animals, including humans. The animals, other than humans, are not particularly limited, and the composition can be used for various livestock, poultry, pets, experimental animals, and the like.
Specific examples of the animals include pigs, cattle, horses, sheep, goats, chickens, wild ducks, ostriches, domestic ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, and the like, but the animals are not limited thereto.

Dose Forms

[138] Dose forms comprising Prevotella bacteria are also provided herein, e.g., for use in methods to treat or prevent a TH2-mediated condition (such as atopic dermatitis and/or a food allergy). A pharmaceutical composition comprising Prevotella bacteria can be formulated as a solid dose form, e.g., for oral administration. The solid dose form can comprise one or more excipients, e.g., pharmaceutically acceptable excipients. The Prevotella bacteria in the solid dose form can be isolated Prevotella bacteria. Optionally, the Prevotella bacteria in the solid dose form can be lyophilized. Optionally, the Prevotella bacteria in the solid dose form are live.
Optionally, the Prevotella bacteria in the solid dose form are gamma irradiated. The solid dose form can comprise a tablet, a minitablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., minitablets comprised in a capsule).

[139] In certain embodiments, the pharmaceutical composition provided herein is prepared as a solid dosage form comprising Prevotella bacteria and a pharmaceutically acceptable carrier.

[140] In some embodiments, the solid dosage form comprises a capsule. The capsule can comprise an enteric coating. The capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. The capsule can comprise Prevotella bacteria powder (e.g., lyophilized Prevotella bacteria).

[141] In some embodiments, the solid dosage form described herein can be, e.g., a tablet or a mini-tablet. In some embodiments, a plurality of mini-tablets can be in (e.g., loaded into) a capsule.

[142] In some embodiments, the solid dosage form comprises a tablet (> 4mm) (e.g., 5mm-17mm). For example, the tablet is a 5mm, 6mm, 7mm, 8mm, 9mm, lOmm, llmm, 12mm, 13mm, 14mm, 15mm, 16mm or 17mm tablet. The size refers to the diameter of the tablet, as is known in the art. As used herein, the size of the tablet refers to the size of the tablet prior to application of an enteric coating.

[143] In some embodiments, the solid dosage form comprises a mini-tablet.
The mini-tablet can be in the size range of 1 mm-4 mm range. E.g., the mini-tablet can be a 1 mm mini-tablet, 1.5 mm mini-tablet, 2 mm mini-tablet, 3 mm mini-tablet, or 4 mm mini-tablet. The size refers to the diameter of the mini-tablet, as is known in the art. As used herein, the size of the minitablet refers to the size of the mini-tablet prior to application of an enteric coating.

[144] The mini-tablets can be in a capsule. The capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. The capsule that contains the mini-tablets can comprise a single layer coating, e.g., a non-enteric coating such as EIPMC (hydroxyl propyl methyl cellulose) or gelatin. The mini-tablets can be inside a capsule: the number of mini-tablets inside a capsule will depend on the size of the capsule and the size of the mini-tablets. As an example, a size 0 capsule can contain 31-35 (an average of 33) mini-tablets that are 3mm mini-tablets.

[145] The solid dosage form (e.g., tablet or mini-tablet) described herein can be enterically coated.

[146] The solid dose form can comprise a coating. The solid dose form can comprise a single layer coating, e.g., enteric coating, e.g., a Eudragit-based coating, e.g., EUDRAGIT L30 D-55, triethylcitrate, and talc. The solid dose form can comprise two layers of coating. For example, an inner coating can comprise, e.g., EUDRAGIT L30 D-55, triethylcitrate, talc, citric acid anhydrous, and sodium hydroxide, and an outer coating can comprise, e.g., EUDRAGIT
L30 D-55, triethylcitrate, and talc. EUDRAGIT is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives.
Eudragits are amorphous polymers having glass transition temperatures between 9 to > 150 C. Eudragits are non-biodegradable, nonabsorbable, and nontoxic. Anionic Eudragit L dissolves at pH
> 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Eudragit RL
and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH? 5, can prevent drug release in saliva.

[147] The solid dose form (e.g., a capsule) can comprise a single layer coating, e.g., a non-enteric coating such as EIPMC (hydroxyl propyl methyl cellulose) or gelatin.

[148] A pharmaceutical composition comprising Prevotella bacteria can be formulated as a suspension, e.g., for oral administration or for injection.
Administration by injection includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration.
For a suspension, Prevotella bacteria can be in a buffer, e.g., a pharmaceutically acceptable buffer, e.g., saline or PBS. The suspension can comprise one or more excipients, e.g., pharmaceutically acceptable excipients. The suspension can comprise, e.g., sucrose or glucose. The Prevotella bacteria in the suspension can be isolated Prevotella bacteria. Optionally, the Prevotella bacteria in the suspension can be lyophilized. Optionally, the Prevotella bacteria in the solid dose form are live.
Optionally, the Prevotella bacteria in the suspension can be gamma irradiated.
Dosa2e

[149] For oral administration to a human subject, the dose of Prevotella bacteria can be, e.g., about 2x106- about 2x1016 particles. The dose can be, e.g., about 1x107-about lx1015, about 1x108- about lx1014, about 1x109- about lx1013, about lx101 - about lx1014, or about 1x108-about 1x1012 particles. The dose can be, e.g., about 2x106, about 2x107, about 2x108, about 2x109, about 1x101 , about 2x101 , about 2x10", about 2x1012, about 2x1013, about 2x1014, or about 1x1015 particles. The dose can be, e.g., about 2x10'4 particles. The dose can be, e.g., about 2x10'2 particles. The dose can be, e.g., about 2x101 particles. The dose can be, e.g., about 1x101 particles. Particle count can be determined, e.g., by NTA.

[150] For oral administration to a human subject, the dose of Prevotella bacteria can be, e.g., based on total protein. The dose can be, e.g., about 5 mg to about 900 mg total protein. The dose can be, e.g., about 20 mg to about 800 mg, about 50 mg to about 700 mg, about 75 mg to about 600 mg, about 100 mg to about 500 mg, about 250 mg to about 750 mg, or about 200 mg to about 500 mg total protein. The dose can be, e.g., about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, or about 750 mg total protein. The dose can be, e.g., about mg total protein. Total protein can be determined, e.g., by Bradford assay or by the BCA
assay.

[151] For administration by injection (e.g., intravenous administration) to a human subject, the dose of Prevotella bacteria can be, e.g., about 1x106- about lx1016 particles. The dose can be, e.g., about 1x107- about lx1015, about 1x108- about lx1014, about 1x109- about lx1013, about lx101 - about lx1014, or about 1x108- about lx1012 particles.
The dose can be, e.g., about 2x106, about 2x107, about 2x108, about 2x109, about lx101 , about 2x101 , about 2x10", about 2x1012, about 2x1013, about 2x1014, or about lx1015 particles. The dose can be, e.g., about lx1015particles. The dose can be, e.g., about 2x10'4 particles. The dose can be, e.g., about 2x1013 particles. Particle count can be determined, e.g., by NTA.

[152] For administration by injection (e.g., intravenous administration), the dose of Prevotella bacteria can be, e.g., about 5 mg to about 900 mg total protein.
The dose can be, e.g., about 20 mg to about 800 mg, about 50 mg to about 700 mg, about 75 mg to about 600 mg, about 100 mg to about 500 mg, about 250 mg to about 750 mg, or about 200 mg to about 500 mg total protein. The dose can be, e.g., about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, or about 750 mg total protein. The dose can be, e.g., about 700 mg total protein. The dose can be, e.g., about 350 mg total protein. The dose can be, e.g., about 175 mg total protein. Total protein can be determined, e.g., by Bradford assay or by the BCA assay.

[153] In certain embodiments, the pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises at least 1 x 1010 total cells (e.g., at least 1 x 1010 total cells, at least 2 x 1010 total cells, at least 3 x 1010 total cells, at least 4 x 1010 total cells, at least 5 x 1010 total cells, at least 6 x 1010 total cells, at least 7 x 1010 total cells, at least 8 x 1010 total cells, at least 9 x 1010 total cells, at least 1 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises no more than 9 x 1011 total cells (e.g., no more than 1 x 1010 total cells, no more than 2 x 1010 total cells, no more than 3 x 1010 total cells, no more than 4 x 1010 total cells, no more than 5 x 1010 total cells, no more than 6 x 1010 total cells, no more than 7 x 1010 total cells, no more than 8 x 1010 total cells, no more than 9 x 1010 total cells, no more than 1 x 1011 total cells, no more than 2 x 1011 total cells, no more than 3 x 1011 total cells, no more than 4 x 1011 total cells, no more than 5 x 1011 total cells, no more than 6 x 1011 total cells, no more than 7 x 1011 total cells, no more than 8 x 1011 total cells) of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 6 x 109 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1010 total cells of the Prevotella bacteria.
In some embodiments, the pharmaceutical composition comprises about 8 x 1010 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1011 total cells the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 3.2 x 1011 total cells the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1010 to about 8 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1010 to about 1.6 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8 x 1010 to about 8 x 1011 total cells of the Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6 x 1011 to about 8 x 1011 total cells of the Prevotella bacteria.

[154] In certain embodiments, provided herein are solid dosage forms comprising the Prevotella bacteria. In some embodiments, the solid dosage form comprises an enteric coating.
In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 8 x 1010 total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 8 x 1010 total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 8 x 1010 total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 8 x 1010 total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 8 x 1010 total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder).

[155] In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated tablet. In some embodiments, the capsule comprises about 8 x 1010 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 1.6 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 3.2 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the capsule comprises about 8 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder).

[156] In some embodiments, the solid dosage form comprises a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 17mm in diameter. In some embodiments, the tablet comprises about 8 x 1010 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 1.6 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 3.2 x 1011 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the tablet comprises about 8 x 10" total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[157] In some embodiments, the solid dosage form comprises a mini-tablet.
In some embodiments, the mini-tablet is enteric coated. In some embodiments, the mini-tablet is from 1 mm to 4mm in diameter. In some embodiments, the mini-tablet (e.g., enteric coated mini-tablet) is a 1 mm 1.5 mm mini-tablet, 2mm mini-tablet, 3mm mini-tablet, or 4mm mini-tablet. In some embodiments, the solid dosage form comprises mini-tablets that comprise about 8 x 1010 total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets that comprise about 1.6 x 10" total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets that comprise about 3.2 x 10" total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets that comprise about 8 x 10" total cells of the Prevotella bacteria (e.g., total dose of a plurality of mini-tablets). In some embodiments, the Prevotella bacteria in the mini-tablets are lyophilized. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) are contained in a capsule. In some embodiments, the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule comprises a non-enteric coating (e.g., EIPMC
(hydroxyl propyl methyl cellulose) or gelatin) (e.g., is coated with a non-enteric coating). In some embodiments, the capsule comprises a non-enteric coating. In some embodiments, the capsule comprises hydroxyl propyl methyl cellulose (1-1PMC). In some embodiments, the capsule comprises gelatin.
In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) that comprise about 8 x 10" total cells of the Prevotella bacteria are contained in a capsule(s), wherein optionally the capsule comprises EIPMC.
Gamma-irradiation

[158] Powders (e.g., of Prevotella bacteria) can be gamma-irradiated at 17.5 kGy radiation unit at ambient temperature.

[159] Frozen biomasses (e.g., of Prevotella bacteria) can be gamma-irradiated at 25 kGy radiation unit in the presence of dry ice.

Th2-mediated conditions

[160] A TH2 (type 2)-mediated condition that can be treated and/or prevented by Prevotella bacteria (e.g., a pharmaceutical composition thereof) includes a condition that involves an increase in interleukin (IL)-4, IL-5, IL-13, IL-19, IL-21, IL-31, IL-33 and/or TSLP
(Thymic Stromal Lymphopoietin) levels (e.g., mRNA or protein levels), e.g., during the onset or course of the disease.

[161] The Prevotella bacteria (e.g., a pharmaceutical composition thereof) can decrease interleukin (IL)-4, IL-5, IL-13, IL-19, IL-21, IL-31, IL-33 and/or TSLP
(Thymic Stromal Lymphopoietin) levels (e.g., mRNA or protein levels), e.g., the Prevotella bacteria (e.g., a pharmaceutical composition thereof) causes a decrease as compared to the level in the absence of (or prior to) administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof). The pharmaceutical composition can decrease the levels, e.g., by about 20%, by about 30%, by about 40%, by about 50%, by about 60%, by about 70%, by about 80%, or by about 90%.

[162] The TH2-mediated condition that can be treated and/or prevented by Prevotella bacteria (e.g., a pharmaceutical composition thereof) includes a condition that involves an increase in IgGl, IgE, and/or IgA levels (e.g., mRNA or protein levels), e.g., during the onset or course of the disease.

[163] The Prevotella bacteria (e.g., a pharmaceutical composition thereof) can decrease IgGl, IgE, and/or IgA levels (e.g., mRNA or protein levels), e.g., the Prevotella bacteria (e.g., a pharmaceutical composition thereof) causes a decrease as compared to the level in the absence of (or prior to) administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof). The pharmaceutical composition can decrease the levels, e.g., by about 20%, by about 30%, by about 40%, by about 50%, by about 60%, by about 70%, by about 80%, or by about 90%.

[164] The TH2-mediated condition can comprise asthma, atopic dermatitis, an eosinophilic disease, or an allergy (e.g., seasonal allergy, pet allergy, or food allergy). The allergy can comprise a food allergy, seasonal allergic rhinitis, or pet allergy. The food allergy can comprise a peanut allergy. The food allergy can comprise a cow's milk, hen egg, fish, crustacean shellfish, tree nut, wheat, or soy allergy. The food allergy can comprise an allergy to a food antigen. The food antigen can comprise a peanut antigen. The food allergy can comprise an allergy to food antigen and the food antigen can comprise a cow's milk, hen egg, fish, crustacean shellfish, tree nut, wheat, or soy antigen.

[165] Some of the particular TH2-mediated conditions are further detailed below.
Allergic Rhinitis

[166] In some embodiments, the TH2-mediated condition includes allergic rhinitis (i.e., hay fever). Allergic rhinitis occurs when an allergen causes inflammation in the nose. Potential allergen types include, individually or in combination, pollens, pet hair, dander, dust mites, mold, smoke, and perfume. Symptoms of allergic rhinitis can include, individually or in combination, runny or stuffy nose; itchy eyes, mouth, throat or skin; sneezing; coughing;
and fatigue.
Asthma

[167] In some embodiments, the TH2-mediated condition includes asthma (e.g., allergic asthma). Asthma occurs when airways, for example in the lungs, are inflamed. A
type of asthma included among the conditions relevant to the disclosures herein is atopic asthma. Symptoms of asthma can include, individually or in combination, coughing, wheezing, shortness of breath, and chest tightness.
Atopic Dermatitis

[168] In some embodiments, the TH2-mediated condition includes atopic dermatitis (i.e., eczema). Atopic dermatitis occurs when the skin is inflamed. It can occur along with allergic rhinitis and/or asthma. Its symptoms can include, individually or in combination, dry skin, redness, itching, rashes, and sores.
Urticaria

[169] In some embodiments, the TH2-mediated condition includes urticaria (i.e., hives) .
Urticaria occurs when the skin develops swollen red welts. The condition can be caused by blood plasma leaking out of vessels due to histamine, for example as a result of an allergic reaction.
The symptoms of urticaria can include, individually or in combination, batches of welts, itching, and swelling.
Angioedema

[170] In some embodiments, the TH2-mediated condition includes angioedema (i.e., deep tissue swelling). When the swelling is beneath the skin, the condition otherwise similar to urticaria can be classified as angioedema. The condition can be caused by blood plasma leaking out of vessels due to histamine, for example as a result of an allergic reaction. The symptoms of angioedema can include, individually or in combination, swelling in the eyes, mouth, hands, feet, or throat; difficulty with breathing; and stomach cramps.
Food Allergies

[171] In some embodiments, the TH2-mediated condition includes a food allergy. Food allergies occur when food (e.g., an allergen thereof) causes an abnormal immune response.
Typical types of food that can cause a reaction include eggs, milk, peanuts, tree nuts (e.g., walnuts), fish, shellfish, wheat, and soy. In addition, seeds (e.g., sesame, mustard), fruits, and rice can also cause food allergies. The symptoms can include, individually or in combination, itching in the mouth; hives; swelling of parts of the body such as the face;
trouble breathing;
abdominal discomfort; and dizziness.
Insect-Induced Allergies

[172] In some embodiments, the TH2-mediated condition includes an insect-induced allergy. An insect-induced allergy occurs when the immune system reacts to an insect sting or bite. Typical types of insect that can cause such a reaction include wasps, bees, hornets, yellow-jackets, ants, mosquitoes, bed bugs, fleas, and ticks.
Drug Allergies

[173] In some embodiments, the TH2-mediated condition includes a drug allergy. Drug allergies occur as an adverse reaction upon exposure to a drug. Some types of drugs that can cause such a reaction include penicillin, sulfonamides, anticonvusants, aspirin, and chemotherapy drugs. Drug allergy symptoms can include, individually or in combination, fever, itching, hives, rash, swelling, and shortness of breath.
Anaphylaxis

[174] In some embodiments, the TH2-mediated condition includes anaphylaxis.

Anaphylaxis occurs when the reaction to food, insect venom, or a drug is severe. It can affect the whole body, and can alter breathing, blood pressure, and heart rate.
Eosinophilia

[175] In some embodiments, the TH2-mediated condition includes eosinophilia (e.g., primary eosinophilia). Eosinophilia occurs when the eosinophil count exceeds certain thresholds at a specific site or in the peripheral blood.

[176] For each of these TH2-mediated conditions, the methods described herein for treating or preventing such conditions can result in lessening, stabilization, or another improvement in the symptoms of the particular TH2-mediated condition being treated, which symptoms include those described herein.
Additional Therapeutic A2ents

[177] In certain aspects, the methods provided herein include the administration to a subject of a bacterium and/or a bacterial composition described herein (e.g., a Prevotella bacteria-containing pharmaceutical composition) either alone or in combination with another therapeutic, e.g., to treat or prevent a TH2-mediated condition (such as atopic dermatitis and/or a food allergy). The pharmaceutical composition comprising Prevotella bacteria can be administered, e.g., in combination with an anti-inflammatory agent. The anti-inflammatory agent can be an anti-histamine (such as cetirizine, fexofenadine, or diphenhydramine), epinephrine, a corticosteroid (oral or topical) (such as betamethasone valerate, hydrocortisone or prednisone), a calcineurin inhibitor (such as tacrolimus or pimecrolimus), cyclosporine, interferon gamma-1 b, or dupilumab. Topical corticosteroids that can be used include: Alclometasone dipropionate, Betamethasone dipropionate, Betamethasone valerate, Clobetasol propionate, Desonide, Desoximetasone Fluocinolone acetonide, Fluocinonide, Fluticasone propionate, Halobetasol propionate, Hydrocortisone, Hydrocortisone butyrate, Hydrocortisone valerate, Mometasone furoate, Triamcinolone acetonide, and Triamcinolone diacetate.

[178] In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the other therapy can be administered to the subject in any order. In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the other therapy are administered conjointly.

[179] In some embodiments, the Prevotella bacteria-containing pharmaceutical composition is administered to the subject before the additional therapeutic is administered (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before). In some embodiments, the Prevotella bacteria-containing pharmaceutical composition is administered to the subject after the additional therapeutic is administered (e.g., at least 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours after or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after). In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the additional therapeutic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other). In some embodiments, the subject is administered an antibiotic before the Prevotella bacteria-containing pharmaceutical composition is administered to the subject (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before). In some embodiments, the subject is administered an antibiotic after the Prevotella bacteria-containing pharmaceutical composition is administered to the subject (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after). In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the antibiotic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other).

[180] In certain embodiments, the subject may undergo surgery. Types of surgery include but are not limited to preventative, diagnostic or staging, curative and palliative surgery.

[181] In some embodiments, the additional therapeutic is an antibiotic.
"Antibiotics"
broadly refers to compounds capable of inhibiting or preventing a bacterial infection. Antibiotics can be classified in a number of ways, including their use for specific infections, their mechanism of action, their bioavailability, or their spectrum of target microbe (e.g., Gram-negative vs. Gram-positive bacteria, aerobic vs. anaerobic bacteria, etc.) and these may be used to kill specific bacteria in specific areas of the host ("niches") (Leekha, et al 2011. General Principles of Antimicrobial Therapy. Mayo Clin Proc. 86(2): 156-167). In certain embodiments, antibiotics can be used to selectively target bacteria of a specific niche. In some embodiments, antibiotics are administered after the bacterial treatment. In some embodiments, antibiotics are administered after the bacterial treatment to remove the engraftment.

[182] In some aspects, antibiotics can be selected based on their bactericidal or bacteriostatic properties. Bactericidal antibiotics include mechanisms of action that disrupt the cell wall (e.g., 0-lactams), the cell membrane (e.g., daptomycin), or bacterial DNA (e.g., fluoroquinolones). Bacteriostatic agents inhibit bacterial replication and include sulfonamides, tetracyclines, and macrolides, and act by inhibiting protein synthesis.
Furthermore, while some drugs can be bactericidal in certain organisms and bacteriostatic in others, knowing the target organism allows one skilled in the art to select an antibiotic with the appropriate properties. In certain treatment conditions, bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics. Thus, in certain embodiments, bactericidal and bacteriostatic antibiotics are not combined.

[183] Antibiotics include, but are not limited to aminoglycosides, ansamycins, carbacephems, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, oxazolidonones, penicillins, polypeptide antibiotics, quinolones, fluoroquinolone, sulfonamides, tetracyclines, and anti-mycobacterial compounds, and combinations thereof.

[184] Aminoglycosides include, but are not limited to Amikacin, Gentamicin, Kanamycin, Neomycin, Netilmicin, Tobramycin, Paromomycin, and Spectinomycin.
Aminoglycosides are effective, e.g., against Gram-negative bacteria, such as Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis, and against certain aerobic bacteria but less effective against obligate/facultative anaerobes.
Aminoglycosides are believed to bind to the bacterial 30S or 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.

[185] Ansamycins include, but are not limited to, Geldanamycin, Herbimycin, Rifamycin, and Streptovaricin. Geldanamycin and Herbimycin are believed to inhibit or alter the function of Heat Shock Protein 90.

[186] Carbacephems include, but are not limited to, Loracarbef.
Carbacephems are believed to inhibit bacterial cell wall synthesis.

[187] Carbapenems include, but are not limited to, Ertapenem, Doripenem, Imipenem/Cilastatin, and Meropenem. Carbapenems are bactericidal for both Gram-positive and Gram-negative bacteria as broad-spectrum antibiotics. Carbapenems are believed to inhibit bacterial cell wall synthesis.

[188] Cephalosporins include, but are not limited to, Cefadroxil, Cefazolin, Cefalotin, Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil,and Ceftobiprole.
Selected Cephalosporins are effective, e.g., against Gram-negative bacteria and against Gram-positive bacteria, including Pseudomonas, certain Cephalosporins are effective against methicillin-resistant Staphylococcus aureus (MRSA). Cephalosporins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[189] Glycopeptides include, but are not limited to, Teicoplanin, Vancomycin, and Telavancin. Glycopeptides are effective, e.g., against aerobic and anaerobic Gram-positive bacteria including MRSA and Clostridium difficile. Glycopeptides are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[190] Lincosamides include, but are not limited to, Clindamycin and Lincomycin.
Lincosamides are effective, e.g., against anaerobic bacteria, as well as Staphylococcus, and Streptococcus. Lincosamides are believed to bind to the bacterial 50S
ribosomal subunit thereby inhibiting bacterial protein synthesis.

[191] Lipopeptides include, but are not limited to, Daptomycin.
Lipopeptides are effective, e.g., against Gram-positive bacteria. Lipopeptides are believed to bind to the bacterial membrane and cause rapid depolarization.

[192] Macrolides include, but are not limited to, Azithromycin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Telithromycin, and Spiramycin.
Macrolides are effective, e.g., against Streptococcus and Mycoplasma.
Macrolides are believed to bind to the bacterial or 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

[193] Monobactams include, but are not limited to, Aztreonam. Monobactams are effective, e.g., against Gram-negative bacteria. Monobactams are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[194] Nitrofurans include, but are not limited to, Furazolidone and Nitrofurantoin.

[195] Oxazolidonones include, but are not limited to, Linezolid, Posizolid, Radezolid, and Torezolid. Oxazolidonones are believed to be protein synthesis inhibitors.

[196] Penicillins include, but are not limited to, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Temocillin and Ticarcillin. Penicillins are effective, e.g., against Gram-positive bacteria, facultative anaerobes, e.g., Streptococcus, Borrelia, and Treponema. Penicillins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[197] Penicillin combinations include, but are not limited to, Amoxicillin/clavulanate, Ampicillin/sulbactam, Piperacillin/tazobactam, and Ticarcillin/clavulanate.

[198] Polypeptide antibiotics include, but are not limited to, Bacitracin, Colistin, and Polymyxin B and E. Polypeptide Antibiotics are effective, e.g., against Gram-negative bacteria.
Certain polypeptide antibiotics are believed to inhibit isoprenyl pyrophosphate involved in synthesis of the peptidoglycan layer of bacterial cell walls, while others destabilize the bacterial outer membrane by displacing bacterial counter-ions.

[199] Quinolones and Fluoroquinolone include, but are not limited to, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, and Temafloxacin.
Quinolones/Fluoroquinolone are effective, e.g., against Streptococcus and Neisseria.
Quinolones/Fluoroquinolone are believed to inhibit the bacterial DNA gyrase or topoisomerase IV, thereby inhibiting DNA replication and transcription.

[200] Sulfonamides include, but are not limited to, Mafenide, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim-Sulfamethoxazole (Co-trimoxazole), and Sulfonamidochrysoidine. Sulfonamides are believed to inhibit folate synthesis by competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.

[201] Tetracyclines include, but are not limited to, Demeclocycline, Doxycycline, Minocycline, Oxytetracycline, and Tetracycline. Tetracyclines are effective, e.g., against Gram-negative bacteria. Tetracyclines are believed to bind to the bacterial 30S
ribosomal subunit thereby inhibiting bacterial protein synthesis.

[202] Anti-mycobacterial compounds include, but are not limited to, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifabutin, Rifapentine, and Streptomycin.

[203] Suitable antibiotics also include arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin/clavulanate, ampicillin/sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin Pl, clarithromycin, erythromycins, furazolidone, fusidic acid, Na fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazoles, mikamycin, mutacin B-Ny266, mutacin B-JH1140, mutacin J-T8, nisin, nisin A, novobiocin, oleandomycin, ostreogrycin, piperacillin/tazobactam, pristinamycin, ramoplanin, ranalexin, reuterin, rifaximin, rosamicin, rosaramicin, spectinomycin, spiramycin, staphylomycin, streptogramin, streptogramin A, synergistin, taurolidine, teicoplanin, telithromycin, ticarcillin/clavulanic acid, triacetyloleandomycin, tylosin, tyrocidin, tyrothricin, vancomycin, vemamycin, and virginiamycin.

[204] In some embodiments, the additional therapy comprises administering a therapeutic bacteria (e.g., Prevotella bacteria) and/or a therapeutic combination of bacteria to the subject so a healthy microbiome can be reconstituted in the subject. In some embodiments the therapeutic bacteria is a probiotic bacteria.

[205] Some of the particular additional therapies are further detailed below.
Allergic Rhinitis

[206] In some embodiments, the TH2-mediated condition includes allergic rhinitis, and the additional therapy includes an agent that can be used to treat allergic rhinitis. Such agents include, individually or in combination, corticosteroids (e.g., prednisone, methylprednisolone, triamcinolone acetonide, betamethasone), antihistamines (e.g., acrivastine, alimemazine, antazoline, astemizole, azelastine, bepotastine, bilastine, bromazine, brompheniramine, carbinoxamine, cetirizine, chlorcyclizine, chloropyramine, chlorphenamine, clemastine, cyclizine, cyproheptadine, desloratadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, ebastine, fexofenadine, hydroxyzine, ketotifen, levocabastine, levocetirizine, loratadine, meclizine, mepyramine, mizolastine, olopatadine, orphenadrine, pheniramine, promethazine, quifenadine, rupatadine, terfenadine, tripelennamine, triprolidine), mast cell stabilizers (e.g., cromolyn), decongestants (e.g., beclomethasone, budesonide, ciclesonide, dexamethasone, ephedrine, flunisolide, fluticasone, fluticasone furoate, fluticasone propionate, levomethamphetamine, mometasone, naphazoline, oxymetazoline, phenylephrine, phenylpropanolamine, prednisolone, propylhexedrine, pseudoephedrine, synephrine, tetryzoline, tixocortol, tramazoline, triamcinolone, triamcinoloneacetonide, xylometazoline), leukatriene receptor antagonists (e.g., montelukast, zafirlukast, zileuton, MR-886, meclofenamate sodium), and immunotherapeutic agents (e.g., containing a form of the allergen itself, containing a form of an antibody such as omalizumab). These agents can also be used for other types of allergies in general, which allergies may occur as the sole type of allergy or may occur in combination with other types of allergies.
Asthma

[207] In some embodiments, the TH2-mediated condition includes asthma (e.g., allergic asthma), and the additional therapy includes an agent that can be used to treat asthma. Such agents include, individually or in combination, the corticosteroids, decongestants (some of which are also corticosteroids), mast cell stabilizers, leukotriene modifiers, and immunotherapeutic agents provided herein for the treatment of allergic rhinitis. In addition, for asthma, the agents also include, individually or in combination, beta-agonists (e.g., salmeterol, formoterol, albuterol, levalbuterol), certain corticosterone & beta-agonist combinations (e.g., fluticasone-salmeterol, budesonide-formoterol, formoterol-mometasone), additional immunotherapeutic agents (e.g., mepolizumab, dupilumab, resulizumab, and benralizumab), and certain other drugs (e.g., theophylline, ipratropium). These agents can be provided via the use of an inhaler, as an injection (e.g., for antibody forms), or as a pill (e.g., as a sublingual tablet for allergen immunotherapy).
Atopic Dermatitis

[208] In some embodiments, the TH2-mediated condition includes atopic dermatitis, and the additional therapy includes an agent that can be used to treat atopic dermatitis. Such agents include, individually or in combination, corticosteroids (e.g., prednisone) and immunotherapeutic agents (e.g., dupilumab) as provided herein for the treatment of allergic rhinitis or asthma. In addition, for atopic dermatitis, the agents also include calcineurin inhibitors (e.g., tacrolimus, pimecrolimus), certain supplements (e.g., vitamin D), immunosuppressants (e.g., ciclosporin, methotrexate, interferon gamma-lb, mycophenolate mofetil, azathioprine), and other drugs (e.g., crisaborole).
Urticaria

[209] In some embodiments, the TH2-mediated condition includes urticaria, and the additional therapy includes an agent that can be used to treat urticaria. Such agents include, individually or in combination, antihistamines (e.g., diphenhydramine, loratadine, fexofenadine, cetirizine, desloratadine), corticosteroids (e.g., prednisone), leukatriene receptor antagonists, and immunotherapeutic agents (e.g., omalizumab) as provided herein for the treatment of allergic rhinitis or asthma. In addition, for urticaria, the agents can also include other antihistamines (e.g., ranitidine, cimetidine, famotidine), immunosuppressants (e.g., ciclosporin, tacrolimus, sirolimus, mycophenolate), anti-inflammatory medications (e.g., dapsone, sulfasalazine, hydroxychloroquine), corticosteroids (e.g., cortisone), and hormones (e.g., epinephrine).
Angioedema

[210] In some embodiments, the TH2-mediated condition includes angioedema, and the additional therapy includes an agent that can be used to treat angioedema.
Such agents include, individually or in combination, antihistamines (e.g., diphenhydramine, loratadine, fexofenadine, cetirizine, desloratadine), corticosteroids (e.g., prednisone), leukatriene receptor antagonists, and immunotherapeutic agents (e.g., omalizumab) as provided herein for the treatment of allergic rhinitis or asthma. In addition, for angioedema, the agents can also include other antihistamines (e.g., ranitidine, cimetidine, famotidine), immunosuppressants (e.g., ciclosporin, tacrolimus, sirolimus, mycophenolate), anti-inflammatory medications (e.g., dapsone, sulfasalazine, hydroxychloroquine), corticosteroids (e.g., cortisone), and hormones (e.g., epinephrine).
Food Allergies

[211] In some embodiments, the TH2-mediated condition includes a food allergy, and the additional therapy includes an agent that can be used to treat food allergies. Such agents include, individually or in combination, epinephrine, antihistamines, glucocorticoid steroids, immunotherapeutic agents (e.g., containing a form of the allergen itself, containing a form of an antibody such as omalizumab).
Insect-Induced Allergies

[212] In some embodiments, the TH2-mediated condition includes an insect-induced allergy, and the additional therapy includes an agent that can be used to treat insect-induced allergies. Such agents include antihistamines.
Drug Allergies

[213] In some embodiments, the TH2-mediated condition includes a drug allergy, and the additional therapy includes an agent that can be used to treat drug allergies. Such agents include, individually or in combination, antihistamines (e.g., diphenhydramine) and corticosteroids.
Anaphylaxis

[214] In some embodiments, the TH2-mediated condition includes anaphylaxis, and the additional therapy includes an agent that can be used to treat anaphylaxis.
Such agents include the same agents that can be used to treat allergies due to food, insect venom, or drugs can be used to treat anaphylaxis (e.g., epinephrine).
Eosinophilia

[215] In some embodiments, the TH2-mediated condition includes eosinophilia (e.g., primary eosinophilia), and the additional therapy includes an agent that can be used to treat eosinophilia. Such agents include corticosteroids (e.g., prednisone).

[216] For each of these TH2-mediated conditions, in some embodiments, the disclosed pharmaceutical compositions can be administered in addition to one or more of these provided additional therapies. For example, the pharmaceutical compositions and an agent of the additional therapy can be co-administered.

[217] Additional agents that can be useful in downregulating pathways involving TH2 cell activation include mepolizumab, lebrikizumab, tralokinumab, GSK3772847, RG6149/AMG282, ANB020, 00000459, BI 671800, AZD1981, A51517499, YM-341619, AS1810722, SB010, resiquimod, imiquimod, and CYT003.
Administration

[218] In certain aspects, provided herein is a method of delivering a Prevotella bacteria-containing pharmaceutical composition described herein to a subject. In some embodiments of the methods provided herein, the composition is administered in conjunction with the administration of an additional therapeutic (e.g., such as an anti-inflammatory agent). In some embodiments, the Prevotella bacteria are co-formulated in a pharmaceutical composition with the additional therapeutic. In some embodiments, the Prevotella bacteria (e.g., a pharmaceutical composition thereof) are co-administered with the additional therapeutic. In some embodiments, the additional therapeutic is administered to the subject before administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof) (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22 or 23 hours before, or about 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days before). In some embodiments, the additional therapeutic is administered to the subject after administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof) (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes after, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours after, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days after). In some embodiments, the same mode of delivery is used to deliver both the Prevotella bacteria (e.g., a pharmaceutical composition thereof) and the additional therapeutic. In some embodiments, different modes of delivery are used to administer the Prevotella bacteria (e.g., a pharmaceutical composition thereof) and the additional therapeutic. For example, in some embodiments, the Prevotella bacteria (e.g., a pharmaceutical composition thereof) are administered orally while the additional therapeutic is administered via injection (e.g., an intravenous and/or intramuscular injection).

[219] In certain embodiments, the pharmaceutical compositions and dosage forms described herein can be administered in conjunction with any other conventional treatment.
These treatments may be applied as necessary and/or as indicated and may occur before, concurrent with or after administration of the pharmaceutical compositions and dosage forms described herein.

[220] The dosage regimen can be any of a variety of methods and amounts, and can be determined by one skilled in the art according to known clinical factors. As is known in the medical arts, dosages for any one patient can depend on many factors, including the subject's species, size, body surface area, age, sex, immunocompetence, and general health, the particular microorganism to be administered, duration and route of administration, the kind and stage of the disease, and other compounds such as drugs being administered concurrently. In addition to the above factors, such levels can be affected by the infectivity of the microorganism, and the nature of the microorganism, as can be determined by one skilled in the art. The dose of the pharmaceutical compositions described herein may be appropriately set or adjusted in accordance with the dosage form, the route of administration, the degree or stage of a condition, and the like. For example, the general effective dose of the agents may range between 0.01 mg/kg body weight/day and 1000 mg/kg body weight/day, between 0.1 mg/kg body weight/day and 1000 mg/kg body weight/day, 0.5 mg/kg body weight/day and 500 mg/kg body weight/day, 1 mg/kg body weight/day and 100 mg/kg body weight/day, or between 5 mg/kg body weight/day and 50 mg/kg body weight/day. The effective dose may be 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, or 1000 mg/kg body weight/day or more, but the dose is not limited thereto.

[221] In some embodiments, the dose administered to a subject is sufficient to prevent the condition, delay its onset, or slow or stop its progression or prevent a relapse of the condition.
One skilled in the art will recognize that dosage will depend upon a variety of factors including the strength of the particular compound employed, as well as the age, species, condition, and body weight of the subject. The size of the dose will also be determined by the route, timing, and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular compound and the desired physiological effect.

[222] Suitable doses and dosage regimens can be determined by conventional range-finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound.
Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. An effective dosage and treatment protocol can be determined by routine and conventional means, starting e.g., with a low dose in laboratory animals and then increasing the dosage while monitoring the effects, and systematically varying the dosage regimen as well.
Animal studies are commonly used to determine the maximal tolerable dose ("MTD") of bioactive agent per kilogram weight. Those skilled in the art regularly extrapolate doses for efficacy, while avoiding toxicity, in other species, including humans.

[223] In accordance with the above, in therapeutic applications, the dosages of the active agents used in accordance with the invention vary depending on the active agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage. Generally, the dose should be sufficient to result in slowing progression, and preferably causing regression, of the condition.

[224] Separate administrations can include any number of two or more administrations (e.g., doses), including two, three, four, five or six administrations. One skilled in the art can readily determine the number of administrations to perform, or the desirability of performing one or more additional administrations, according to methods known in the art for monitoring therapeutic methods and other monitoring methods provided herein. In some embodiments, the doses may be separated by at least 1,2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days or 1, 2, 3, or 4 weeks.
Accordingly, the methods provided herein include methods of providing to the subject one or more administrations of a bacterium, where the number of administrations can be determined by monitoring the subject, and, based on the results of the monitoring, determining whether or not to provide one or more additional administrations. Deciding on whether or not to provide one or more additional administrations can be based on a variety of monitoring results, including, but not limited to, subject's anti-bacterium antibody titer, the overall health of the subject and/or the weight of the subject.

[225] The time period between administrations can be any of a variety of time periods.
The time period between administrations can be a function of any of a variety of factors, including monitoring steps, as described in relation to the number of administrations, the time period for a subject to mount an immune response and/or the time period for a subject to clear the bacteria from normal tissue or from the gut. In one example, the time period can be a function of the time period for a subject to mount an immune response; for example, the time period can be more than the time period for a subject to mount an immune response, such as more than about one week, more than about ten days, more than about two weeks, or more than about a month; in another example, the time period can be less than the time period for a subject to mount an immune response, such as less than about one week, less than about ten days, less than about two weeks, or less than about a month. In another example, the time period can be a function of the time period for a subject to clear the bacteria from normal tissue or from the gut;
for example, the time period can be more than the time period for a subject to clear the bacteria from normal tissue or from the gut, such as more than about a day, more than about two days, more than about three days, more than about five days, or more than about a week.

[226] In some embodiments, the delivery of an additional therapeutic in combination with the Prevotella bacteria (e.g., a pharmaceutical composition thereof) described herein reduces the adverse effects and/or improves the efficacy of the additional therapeutic.

[227] The effective dose of an additional therapeutic described herein is the amount of the therapeutic agent that is effective to achieve the desired therapeutic response for a particular patient (e.g., subject), composition, and mode of administration, with the least toxicity to the patient. The effective dosage level can be identified using the methods described herein and will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions administered, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. In general, an effective dose of an additional therapy will be the amount of the therapeutic agent which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.

[228] The toxicity of an additional therapy is the level of adverse effects experienced by the subject during and following treatment. Adverse events associated with therapy toxicity include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, alopecia, anaphylaxis, anemia, anxiety, lack of appetite, arthralgias, asthenia, ataxia, azotemia, loss of balance, bone pain, bleeding, blood clots, low blood pressure, elevated blood pressure, difficulty breathing, bronchitis, bruising, low white blood cell count, low red blood cell count, low platelet count, cardiotoxicity, cystitis, hemorrhagic cystitis, arrhythmias, heart valve disease, cardiomyopathy, coronary artery disease, cataracts, central neurotoxicity, cognitive impairment, confusion, conjunctivitis, constipation, coughing, cramping, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, dyspepsia, dyspnea, edema, electrolyte imbalance, esophagitis, fatigue, loss of fertility, fever, flatulence, flushing, gastric reflux, gastroesophageal reflux disease, genital pain, granulocytopenia, gynecomastia, glaucoma, hair loss, hand-foot syndrome, headache, hearing loss, heart failure, heart palpitations, heartburn, hematoma, hemorrhagic cystitis, hepatotoxicity, hyperamylasemia, hypercalcemia, hyperchloremia, hyperglycemia, hyperkalemia, hyperlipasemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hyperpigmentation, hypertriglyceridemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypochloremia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, impotence, infection, injection site reactions, insomnia, iron deficiency, itching, joint pain, kidney failure, leukopenia, liver dysfunction, memory loss, menopause, mouth sores, mucositis, muscle pain, myalgias, myelosuppression, myocarditis, neutropenic fever, nausea, nephrotoxicity, neutropenia, nosebleeds, numbness, ototoxicity, pain, palmar-plantar erythrodysesthesia, pancytopenia, pericarditis, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pneumonia, pneumonitis, proteinuria, pulmonary embolus, pulmonary fibrosis, pulmonary toxicity, rash, rapid heartbeat, rectal bleeding, restlessness, rhinitis, seizures, shortness of breath, sinusitis, thrombocytopenia, tinnitus, urinary tract infection, vaginal bleeding, vaginal dryness, vertigo, water retention, weakness, weight loss, weight gain, and xerostomia. In general, toxicity is acceptable if the benefits to the subject achieved through the therapy outweigh the adverse events experienced by the subject due to the therapy.

[229] In some embodiments, the administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof) treats the condition.

[230] As described herein, the condition to be treated can comprise a TH2-mediated condition, such as atopic dermatitis, and/or a food allergy.
EXAMPLES
Example 1: Effects of Prevotella histicola in FITC-driven contact hypersensitivity model.

[231] Exposure of skin to an antigen can, over time, lead to an allergic response to that antigen, for example, in the form of a skin allergy (e.g. dermatitis or atopic dermatitis or eczema) and/or in the form of a food allergy (see e.g. Han et al. The atopic march:
current insights into skin barrier dysfunction and epithelial cell-derived cytokines. Immunol. Rev.
2017.
July;278(1):116-130. Doi: 10.1111/imr.12546; Kawasaki et al. Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized mice. Allergy. 2018.
June;73(6):1313-1321.
Doi: 10.1111/a11.13404; Martel et al. Translational animal models of atopic dermatitis for preclinical studies. Yale J. Biol. Med. 2017. Sept;90(3):389-402; Jin et al.
Animal models of atopic dermatitis. J. Invest. Dermatol. 2009. Jan: 129(1):31-40. Doi 10.1038/jid.2008.106).

[232] The effects of Prevotella histicola Strain B 50329 were studied in a fluorescein isothiocyanate (FITC)-driven contact hypersensitivity model (See e.g. Li et al. T-helper type-2 contact hypersensitivity of Balb/c mice aggravated by dibutyl phthalate via long-term dermal exposure. Feb. 3, 2014. https://doi.org/10.1371/journal.pone.0087887; Imai et al. Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate. Clin. Exp. Allergy. 2006 Nov; 36(11): 1462-8; Dearman et al.
Role of CD4+ T
helper 2-type cells in cutaneous inflammatory responses induced by fluorescein isothiocynate.
Immunology. 2000 Dec; 101(4):442-451. Doi: 10.1046/j.1365-2567.2000.01126.x).

[233] Prevotella histicola strain B 50329 was administered by oral gavage, and the effects of Prevotella histicola on inflammation were analyzed using various read-outs.

[234] The studies were conducted using microbes reconstituted from powder (e.g. in a lyophilized form). Sucrose was used as the vehicle for reconstitution.

[235] Every day of gavage, one vial of the Prevotella histicola strain B
50329 and one vial of anaerobic sucrose was collected from a refrigerator. Anaerobic sucrose was used to prepare the proper bacterial dilutions into sterile tubes. For instance, 800u1 of sucrose was added to 80mg of Prevotella histicola Strain B 50329. In order to ensure proper resuspension, vials of resuspended powder were vortexed so that no powder was stuck to the vial. The mice were gavaged with resuspended powder at the amount of 100 IA per mouse immediately after vortexing (before the powder settles down) and the remaining powder mixture was discarded (a freshly prepared dilution must be used every time). Negative control mice were orally gavaged with 100u1 of vehicle per day.
FITC-driven hypersensitivity Study Protocol:

[236] Mice were purchased from Taconic and allowed to acclimate to the vivarium for at least 1 week prior to the start of the experiment. Mice were housed at 5 animals (or fewer) per cage, with each cage constituting a different treatment group.

[237] On day 0, mice were anesthetized with isoflurane (one at a time) and their backs were shaved.

[238] On day 1, a solution of 0.5 % FITC (w/v) was dissolved in adjuvant (dibutyl phthalate (DBP)) and acetone (1:1). To prepare the 0.5 % FITC, 250mg FITC was dissolved in 25m1 acetone. Once completely dissolved, 25m1 of DBP was added and mixed by vortexing.

[239] On days 1 and 2, mice were sensitized on the back by applying IA of the 0.5 %
FITC solution with a pipette. Anaerobic sucrose served as the negative control. Dexamethasone served as the positive control (Dexamethasone stock solution was prepared by resuspending 25mg of dexamethasone (Sigma) in 1.6 ml of 96% ethanol).

[240] On days 1-6, mice were orally gavaged with vehicle (negative control, group 1) or Prevotella histicola strain B 50329 (group 3), or injected intraperitoneally (i.p.) with Dexamethasone (positive control, group 2) according to following study design:
Group Sensitization Challenge Test substance p.o.
0.5% FITC 0.5% (treatment days 1-6) in 400 [IL FITC in 20u1 1 (n=5) Day 1, 2 Day 6 Vehicle (anerobic sucrose) 2 (n=5) Day 1, 2 Day 6 Dexamethasone (lmg/kg) 3 (n=5) Day 1, 2 Day 6 Prevotella histicola strain B
50329 DS (10mg) DS = Drug substance (freeze-dried)

[241] In addition to the daily gavage (groups 1 and 3) and i.p. injection (group 2), the mice were FITC-challenged on day 6 as follows: On day 6, each mouse was anesthetized with isoflurane and a baseline left ear measurement was obtained using calipers, and then 20 IA of 0.5% FITC solution was applied on the left ear (20111 0.5% FITC (w/v) DBP:acetone (1:1) ("ear challenge" or "FITC challenge").

[242] On day 7, an 8-hour post ear challenge measurement was obtained using calipers.
Mice were euthanized and ears were collected for downstream mRNA analyses using TaqMan RNA-to-CT 1-Step Kit (Applied Biosystems, ThermoFisher Scientific Catalog#
4392653) according to manufacturer's instructions.

[243] Results are shown in Figures 1A and 1B.

[244] Oral administration of Prevotella histicola Strain B 50329 (labeled as "Prevotella histicola" in the Figures 1A-1B) significantly reduced ear swelling at 8h post-FITC ear challenge (Figure 1A).

[245] Compared to the vehicle group, Prevotella histicola Strain B 50329 treatment reduced gene expression for IL-4, IL-5, IL-33, IL-17a, and TSLP in the ears (Figure 1B).
Example 2: Effects of Prevotella histicola in FITC-driven contact hypersensitivity model.

[246] The effect of Prevotella histicola Strain B 50329 in a FITC-driven contact hypersensitivity model was tested against two other strains, Strain 1 and Strain 2, where Strain 1 is a strain of a Prevotella species other than histicola, and Strain 2 is Strain 2 is a strain of a different genus than Prevotella.

[247] As described in Example 1, on day 0, mice were anesthetized with isoflurane and their backs were shaved. On days 1 and 2, mice were sensitized on the back by applying 400 IA
of 0.5 % FITC solution with a pipette. On days 1-6, mice were orally gavaged with vehicle (sucrose) or the tested bacterial strain, or injected intraperitoneally (i.p.) with Dexamethaose (positive control).

[248] As described in Example 1, on day 6, each mouse was anesthetized with isoflurane and a baseline left ear measurement was obtained using calipers.
Then the mice were FITC-challenged with 20[11 of 0.5% FITC solution applied to the left ear.

[249] On day 7, just eight (8) hours following challenge, mice were euthanized for a post-challenge ear measurement using calipers.

[250] Results are shown in Figure 2. Oral administration of Prevotella histicola Strain B 50329 (labeled as "Prevotella histicola" in Figure 2) significantly reduced ear swelling at 8 hours post-FITC challenge, while two other bacterial strains (Strain 1 and Strain 2) did not (Figure 2). The difference in ear swelling between Prevotella histicola Strain B 50329 and Strain 1 (a strain of another species of Prevotella) was not statistically significant, while the difference in ear swelling between Prevotella histicola Strain B 50329 and Strain 2 (strain of another genus than Prevotella) was statistically significant.
Example 3: Effects of Prevotella histicola in a MC903 model of dermatitis-associated food allergy to e22 white protein Ovalbumin (OVA).

[251] A mouse model of dermatitis-associated food allergy was used to assess the efficacy of bacterial strains in modulating an allergic reaction.

[252] MC903, a Vitamin D3 analog, induces inflammation and has been used in a model of atopic dermatitis (See e.g. Hussain et al. Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy. 2017.
American Academy of Allergy, Asthma & Immunol. http://dx. doi. org/10.1016/j . j aci.2017. 02. 035;
Moosbrugger-Martinz et al. A mouse model for atopic dermatitis using topical application of Vitamin D3 or of its analog MC903. Methods Mol. Biol. 2017;1559:91-106; Li et al. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. PNAS. Aug. 1, 2006. Vol.
103(31): 11736-11741)).

[253] MC903 can be used to cutaneously sensitize mice to an antigen of interest, resulting in skin sensitization typified by TSLP and IL-4 production (See e.g.
Noti et al.
Exposure to food allergens through inflamed skin promotes intestinal food allergy via the TSLP-basophil axis. J. Allergy Clin. Immunol. 2014 May; 133(5): 1390-1399.e6). The study design for the MC903 model of dermatitis-associated food allergy is shown in Figure 3A.
Allergens to be tested (e.g. OVA) may be obtained from vendors such as Invivogen or Sigma.
Materials and Methods

[254] Female BALB/c mice (6-8 weeks old) were purchased from Taconic Farms.

Animals were housed in specific pathogen¨free conditions in a vivarium (5 mice or fewer than 5 mice per cage), and all experiments were performed under Institutional Animal Care and Use Committee (IACUC) approved protocols and guidelines. Mice were allowed to acclimate in the vivarium for one week prior to the start of the experiment. PicoLab Rodent Diet 20 is provided and autoclaved water via sipper bottle, given ad libitum and checked daily.

[255] To induce a mouse model mimicking egg food allergy, mice were exposed to MC903 (Tocris) and 100 lig ovalbumin (OVA) daily for 14 consecutive days (days 1-14). 45[IM
of MC903 in 20 [IL of 100% ethanol was applied to one ear by pipette and, once the ear was dried, 100[Ig of OVA in PBS was applied. 20 [IL ethanol was applied to the ears of the vehicle control group.

[256] For the daily oral gavage treatments (days 1-17), negative control mice received vehicle (frozen sucrose) and positive control mice received Tofacitinib (20mg/kg in 100u1/mouse in 0.5% methylcellulose (p.o.); Tocris). One group of mice received 10mg Prevotella histicola Strain B 50329 daily (3.13E+09 TCC/dose), while other groups received 10mg of either Strain A
(1.23E+10 TCC/dose) or Strain B (7.83E+09 TCC/dose) (bacterial strains that were not Prevotella histicola Strain B 50329¨Strain A was a strain of another genus than Prevotella, and Strain B was another strain of Prevotella histicola). On day 15, mice were challenged by oral gavage (p.o., also referred to as intragastric (i.g.)) with 50 mg of OVA.

[257] On day17.5, mice were orally challenged a second time with 50 mg of OVA. Ear inflammation was measured using calipers following the second challenge.

[258] Ear inflammation on Day 18 is shown in Figure 3B (12 hours after the second OVA challenge). Treatment with Prevotella histicola Strain B 50329 (labeled as "P. histicola" in Figures 3B-3D) significantly reduced ear inflammation compared to the negative control group.

[259] On Day 18, 12 hours after the second OVA challenge, mice were euthanized.
Blood (for serum) and tissues (e.g. spleen, draining cervical lymph nodes, mesenteric lymph nodes and ears) were collected for ex vivo processing.

[260] Serum was analyzed by ELISA for anti-OVA IgG1 , anti-OVA IgE using the Chondrex, Inc. Mouse Anti-OVA IgG1 Antibody Assay Kit (Catalog# 3013) and Mouse Anti-OVA IgE Antibody Assay Kit (Catalog# 3010). Results are shown in Figure 3C.

[261] Ears were homogenized for cytokine detection. Spleen, mesenteric lymph nodes (mLN), and cervical lymph nodes (cLN) were analyzed for cytokine expression following in vitro PMA stimulation and supernatant collection. Single cell suspensions of tissues were prepared, counted, and plated at 200,000 cells/well and restimulated with PMA/Ionomycin (eBiosciences Cell Stimulation cocktail Catalog# 00-4975) for 48 hours per manufacturer's instructions. Supernatants were collected and used for downstream multiplex ELISAs to determine cytokine levels using Meso Scale Discovery (MSD) kits (Catalog# K1 5068L-2). Also, ears were dissociated in 250u1 T-PER buffer (Thermo Scientific Catalog# 78510) containing Halt Protease (Thermo Scientific Catalog# 78444) and protein concentrations quantified using the BCA kit (Thermo Scientific Catalog #23227). 10Oug of protein was used to quantify cytokine levels using MSD kits (Catalog# K15068L-2). Results are shown in Figure 3D.
Example 4: Effects of Prevotella histicola in MC903 model of type 2 (Th2) immune response in OVA and food allergy to complete peanut protein (CPE).

[262] To induce a mouse model mimicking egg food allergy and peanut allergy, mice were sensitized to food allergens as described in Example 3 and as depicted in Figure 4A.

[263] MC903 was prepared in Et0H and applied daily as shown (days 1 thru 14).

[264] Some mice were exposed to MC903 and 10Oug OVA in PBS daily for 14 consecutive days. Other mice were exposed to MC903 and 10Oug complete peanut protein (CPE) daily for 14 consecutive days. In addition to the application of antigen (e.g.
OVA or CPE), mice were gavaged with sucrose vehicle (negative control), Tofacitinib (positive control), bacterial Strain A (10mg/dose) or Prevotella histicola Strain B 50329 (10mg/dose).
Strain A is a strain of another genus than Prevotella.

[265] On day 15, mice were challenged by oral gavage with either 50mg of OVA or 50mg peanut powder.

[266] On day17.5, mice were challenged a second time by oral gavage with either 50mg of OVA or 50mg complete peanut powder (CPE).

[267] On Day 18, 12 hours after the final antigen challenge, ear thickness was measured. Mice were euthanized and serum and tissues were collected as described in Example 3.

[268] As shown in Figure 4B, Prevotella histicola Strain B 50329 (labeled "P.
histicola" in Figures 4B-4D) significantly reduced ear inflammation compared to the vehicle control groups in both the OVA and peanut allergy (CPE) groups. Antibody analyses (anti-OVA
IgG1 and anti-OVA IgE) were conducted as described in Example 3 and results shown in Figure 4C. Cytokine analyses were conducted as described in Example 3 and are shown in Figure 4D.
Ear RNA was measured as described in Example 1 and results are shown in Figure 4E.
Example 5: MC903-driven atonic dermatitis and anaphylaxis.

[269] To induce a mouse model mimicking egg food allergy, peanut allergy, and/or other allergen of interest, mice are sensitized to food allergens as described in Example 3 and depicted in Figure 5.

[270] MC903 is prepared in Et0H and applied daily as shown (days 1 thru 14).

[271] Some mice are exposed to MC903 and 10Oug CPE in PBS daily for up to consecutive days. In addition to the application of the model antigen (e.g.
CPE), mice are gavaged with sucrose vehicle (negative control), Tofacitinib (positive control; 100111 orally, daily), bacterial Strain A (10mg/dose) or Prevotella histicola Strain B 50329 (10mg/dose), or 200 g/mouse anti-IL-4 (i.p. days 3, 6, 9 and 12; BioXcell) (days 1-17 or as long as days 1-30).

[272] On day 30, mice are challenged with 500ug CPE i.p. and observed for anaphylaxis. Thirty minutes following CPE challenge, body temperature is measured using a rectal thermometer.

[273] On Day 31, mice are sacrificed and ear inflammation is measured.
Spleen, ear, and lymph tissue cytokines are analyzed using methods described in Examples 1 and 3.
Example 6: Tape-stripping peanut allergy model.

[274] As described above, there are various animal models for studying food allergy.
Some of these models induce sensitization of allergen (e.g. antigen) through skin barrier defects (see e.g. Ohsaki et al. Maternal IgG immune complexes induce food allergen-specific tolerance in offspring. J Exp Med. 2018. 215:91-113; Kanagaratham et al. Experimental models for studying food allergy. Cell Mol Gastroenterol Hepatol. 2018. 6(3):356-369.el.
Doi:
10.1016/j.jcmgh.2018.05.010). In some models, skin barrier defects are induced by repeated tape-stripping of the skin after fur shaving, and the allergen is applied to the resultantly damaged skin. This "epicutaneous sensitization" to the allergen is followed, at some timepoint, by intragastric challenge to the allergen. For example, mice can be sensitized on the ear or back, using tape-stripping and exposure to peanut antigen on either days 1, 2, and 3 (ear sensitization), or days 0, 3, and 6 (back sensitization), as shown in Figure 6A. For the ear sensitization groups, mice are tape-stripped only on day 0, while the back sensitization groups are tape-stripped on days 0, 3, and 6. Mice may be challenged on day 21 and, shortly thereafter, observed and/or sacrificed for various read-outs including, but not limited to, measuring serum peanut-specific IgE, IgGl, and IgA, as well as total IgE, IgGl, and IgA, body temperature, anaphylaxis scoring, diarrhea scoring, and/or ex vivo restimulation of mesenteric lymph node (MLN) cells to assess various cytokines (including IL-4, IL-5, and TSLP). Alternatively, serum may be collected at day 35 (see Figure 6B), and in other instances, a study may last as long as 65 days (see Figure 6C).
Mice may be scored for anaphylaxis and diarrhea as shown in Table 3 and Table 4, respectively.
Table 3: Anaphylaxis Scoring Score Criteria 0 No symptoms 1 Scratching/rubbing around nose and mouth 2 Puffiness around eyes and mouth; diarrhea; pilar erecti; reduced activity with increased respiratory rate 3 Wheezing/labored respiration; cyanosis around mouth and tail.
4 No activity after prodding or tremor and convulsions Table 4: Diarrhea Scoring Score Description 0 No changes 1 Soft but well formed 2 Soft; non-formed 3 One episode of liquid diarrhea 4 At least two episodes of liquid diarrhea

[275] Female BALB/c mice were purchased from Taconic Farms and all experiments performed under Institutional Animal Care and Use Committee (IACUC) approved protocols and guidelines.

[276] Mice were allowed to acclimate in the vivarium for one week prior to the start of the experiment. All mice are housed at 5 animals per cage or less, in individually ventilated cages with standard bedding and enrichment. PicoLab Rodent Diet 20 was provided and autoclaved water via sipper bottle was given ad libitum and checked daily.
Experimental Design

[277] Animal groups were separated as follows (5 mice/group):

[278] 1) Naive mice (no sensitization, no peanut challenge);

[279] 2) Naive mice (no sensitization, peanut challenge on day 21);

[280] 3) Ear sensitization (sensitized days 1, 2, and 3) (no challenge);

[281] 4) Ear sensitization (sensitized days 1, 2, and 3) (peanut challenge on day 21);

[282] 5) Ear sensitization (sensitized days 1, 2, and 3) (Tofacitinib 20mg/kg) (peanut challenge on day 21);

[283] 6) Ear sensitization (sensitized days 1, 2, and 3) (P. histicola 10mg) (peanut challenge day 21);

[284] 7) Back sensitization (sensitized days 0, 3, and 6) (no challenge);

[285] 8) Back sensitization (sensitized days 0, 3, and 6) (peanut challenge on day 21);

[286] 9) Back sensitization (sensitized days 0, 3, and 6) (Tofacitinib 20mg/kg) (peanut challenge on day 21); and

[287] 10) Back sensitization (sensitized days 0, 3, and 6) (Prevotella histi cola Strain B
50329 10mg) (peanut challenge on day 21).

[288] On Day 0, mice were anesthetized with isoflurane, one by one. For the ear sensitization groups, the ears of each mouse were repeatedly tape-stripped (approximately 7-8 times) with cellophane tape. For the back sensitization groups, the backs were shaved and tape-stripped with cellophane tape (approximately 7-8 times).

[289] For the ear sensitization groups, mice were tape-stripped on day 0.
On days 1, 2, and 3, 25 IA of the peanut protein solution (4mg/m1 peanut protein in PBS) was applied to both ears with a cotton swab.

[290] For the back sensitization groups, on days 0, 3, and 6, mice were tape-stripped and 100[Ig of peanut protein applied. The sensitized area was covered with a new waterproof bandage each time.

[291] For the Prevotella histicola Strain B 50329 groups, mice were orally gavaged with 10mg bacteria on days 1 through 21.

[292] On Day 21, mice from groups 2, 4, 5, 6, 8, and 9 were challenged with a gavage of 100mg peanut protein. Mice from all groups were cheek bled one hour following peanut protein challenge and blood collected for total IgE, peanut-specific IgE, total IgG1 , peanut-specific IgGl, total IgA, and peanut-specific IgA ELISAs (Chondrex, per manufacturer's instructions).

[293] Inflammation results are shown in Figure 6D. For both the ear groups and the back groups, Prevotella histicola Strain B 50329 (labeled "P. histicola" in Figures 6D-6I) decreased inflammation.

[294] Total and peanut-specific serum IgE, and IgG1 levels from the day of challenge are shown in Figures 6E and 6F, respectively.

[295] Total and peanut-specific serum IgE, IgGl, and IgA levels from 2 weeks post-challenge are shown in Figures 6G, 6H, and 61, respectively.
Example 7: FITC-CHS model.

[296] Prevotella histicola Strain B 50329 was tested in a FITC-CHS model as shown in Figure 7A. The dose tested was 4.69E+09 TCC.

[297] The effects of Prevotella histicola Strain B 50329 on TH2 cytokines (IL-13, IL-4, IL-5, IL-31, and IL-33) were examined at day 7. As shown in Figure 7B, Prevotella histicola Strain B 50329 (labeled as "Prevotella histicola" in Figures 7B-7C) significantly lowered levels of IL-13, IL-5, and IL-31 in gut draining mesenteric lymph nodes. Cytokine levels were determined by MSD, with the experiment performed as described in Example 3. As shown in Figure 7C, Prevotella histicola Strain B 50329 treatment significantly lowered levels of IL-13 in ear draining cervical lymph nodes. The experiment was performed as described in Example 3.

[298] This example demonstrates that Prevotella histicola Strain B 50329 treatment significantly lowered TH2 cytokine secretion in the PMA/ionomycin ex vivo re stimulated cells from gut draining mesenteric lymph nodes and the ear draining cervical lymph nodes.

Example 8: MC903 driven Atopic Dermatitis.

[299] Prevotella histicola Strain B 50329 was tested in an MC903 driven atopic dermatitis model as shown in Figure 8A.

[300] For these experiments, mice were purchased from Taconic Labs and allowed to acclimate in the vivarium for 1 week prior to start of experiment. Mice were housed 5 animals per cage, in individually ventilated cages with standard bedding and enrichment. Standard Purina rodent diet (5001) and autoclaved water was provided ad libitum and checked daily.

[301] On Day 1, mice were anesthetized, and a baseline ear measurement was taken.
While anesthetized, ears were then sensitized with 45 nIVI calcipitriol (MC903) by pipetting a total of 20uL of solution onto both dorsal and ventral sides of the ear. Ears were sensitized daily for 14 days.

[302] Mice were orally gavaged daily with Prevotella histicola Strain B
50329 at a dose of 4.69E+09 TCC, or positive control (tofacitinib), QD, from Day 1 through Day 14.

[303] Ear measurements were taken throughout the study to track changes in thickness over time and day 14 to determine change in ear thickness from baseline.

[304] Ex vivo experiments were performed on day 17.

[305] MC903 preparation protocol: 10mg calcipitriol powder was dissolved in 10 mL
99% ethanol to create 1 mg/mL stock. Stock was diluted to 0.01856 mg/mL in 99%
ethanol. The diluted solution was aliquoted into daily use, light protective tubes at -20 C.

[306] Positive control ¨ Tofacitinib preparation: Tofacitinib was prepared in 0.5% (w/v) methylcellulose. Purified water was brought to a boil on a stir/heat plate. An appropriate amount of powder methylcellulose was weighed out. The boiling water was stirred and powder methylcellulose was added. Stirring was continued until powder was incorporated into the water.
The mixture was allowed to cool overnight in 4 C while stirring on stir plate.
50 mg stock of Tofacitinib was resuspended in 0.5% MC (mixture formed a suspension).
Tofacitinib was administered p.o., 100 uL per mouse.
Results:

[307] As shown in Figure 8B, Prevotella histicola Strain B 50329 (labeled as "Prevotella histicola" in Figures 8B-8E) treatment resulted in reduced ear inflammation in MC903 driven atopic dermatitis, as determined by ear measurements over time (left panel) and ear inflammation on day 14 (right panel).

[308] The effects of of Prevotella histicola Strain B 50329 on TH2 cytokine transcript levels (Tslp, 115, 1131, 114, Cc119, and Ccr4) in ear tissue were examined at day 17. As shown in Figure 8C, Prevotella histicola Strain B 50329 treatment significantly lowered levels of 115, 1131, and Ccr4 transcripts in ear tissue, as determined by qPCR.

[309] The effects of Prevotella histicola Strain B 50329 on mast cell related gene transcript levels (Mcpt 1) in the jejunum were examined at day 17. The results in Figure 8D
demonstrate that Prevotella histicola Strain B 50329 significantly reduced Mcpatranscript levels in the jejunum of mice in the MC903-driven atopic dermatitis model, as determined by qPCR

[310] The effects of Prevotella histicola Strain B 50329 on IL-10 levels in mesenteric lymph nodes and spleen were examined at day 17. As shown in Figure 8E, Prevotella histicola Strain B 50329 treatment resulted in significantly increased IL-10 levels in mesenteric lymph nodes and spleen mice upon ex vivo re-stimulation with PMA/Ionomycin in tissue isolated from the MC903-driven atopic dermatitis model, as determined by MSD. The experiment was performed as described in Example 3.

[311] The results in this example demonstrate that ear inflammation in MC903-driven atopic dermatitis was significantly reduced with Prevotella histicola Strain B
50329 treatment compared to vehicle treated mice.

[312] Prevotella histicola Strain B 50329 treatment showed decreases in TH2 cytokine transcripts in ear tissue and a mast cell related transcript (Mcptl) in the jejunum.

[313] Prevotella histicola Strain B 50329 treatment showed increased levels of IL-10 in gut draining mesenteric lymph nodes and spleen cells upon ex vivo re-stimulation with PMA/Ionomycin.
Incorporation by Reference

[314] All publications patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

Equivalents

[315] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims (235)

What is claimed is:

1. A method of treating or preventing a TH2-mediated condition in a subject comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria.

2. The method of claim 1, wherein the subject is a human subject.

3. The method of claim 1 or claim 2, wherien at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial-derived content of the pharmaceutical composition is derived from Prevotella bacteria.

4. The method of any one of claims 1 to 3, wherein the method treats the TH2-mediated condition.

5. The method of any one of claims 1 to 4, wherein the TH2-mediated condition is asthma, atopic dermatitis, an eosinophilic disease, and/or an allergy.

6. The method of claim 5, wherein TH2-mediated condition is an allergy, and the allergy is a food allergy, seasonal allergic rhinitis, and/or a pet allergy.

7. The method of claim 5, wherein the TH2-mediated condition is atopic dermatitis.

8. The method of claim 5, wherein the TH2-mediated condition is a food allergy.

9. The method of claim 8, wherein the food allergy is a peanut, cow's milk, hen egg, fish, crustacean shellfish, tree nut, wheat, or soy allergy.

10. The method of claim 8, wherein the food allergy is a peanut allergy.

11. The method of claim 8, wherein food allergy is an allergy to a food antigen.

12. The method of claim 11, wherein the food antigen is a peanut antigen, a cow's milk antigen, a hen egg antigen, a fish antigen, a crustacean shellfish antigen, a tree nut antigen, a wheat antigen, or a soy antigen.

13. The method claim 11, wherein the food antigen is a peanut antigen.

14. The method of any one of claim 1 to 13, wherein the method results in a decrease in interleukin (IL)-4 levels in the subject.

15. The method of claim 14, wherein the IL-4 levels are IL-4 protein levels or IL-4 mRNA
levels.

16. The method of any one of claim 1 to 15, wherein the method results in a decrease in interleukin (IL)-5 levels in the subject.

17. The method of claim 16, wherein the IL-5 levels are IL-5 protein levels or IL-5 mRNA
levels.

18. The method of any one of claim 1 to 17, wherein the method results in a decrease in interleukin (IL)-13 levels in the subject.

19. The method of claim 18, wherein the IL-13 levels are IL-13 protein levels or IL- 13 mRNA levels.

20. The method of any one of claim 1 to 19, wherein the method results in a decrease in interleukin (IL)-19 levels in the subject.

21. The method of claim 20, wherein the IL-19 levels are IL-19 protein levels or IL- 19 mRNA levels.

22. The method of any one of claim 1 to 21, wherein the method results in a decrease in interleukin (IL)-21 levels in the subject.

23. The method of claim 22, wherein the IL-21 levels are IL-21 protein levels or IL-21 mRNA levels.

24. The method of any one of claim 1 to 23, wherein the method results in a decrease in interleukin (IL)-31 levels in the subject.

25. The method of claim 24, wherein the IL-31 levels are IL-31 protein levels or IL-31 mRNA levels.

26. The method of any one of claim 1 to 25, wherein the method results in a decrease in interleukin (IL)-33 levels in the subject.

27. The method of claim 26, wherein the IL-33 levels are IL-33 protein levels or IL-33 mRNA levels.

28. The method of any one of claim 1 to 27, wherein the method results in a decrease in Thymic Stromal Lymphopoietin (TSLP) levels in the subject.

29. The method of claim 28, wherein the TSLP levels are TSLP protein levels or TSLP
mRNA levels.

30. The method of any one of claim 1 to 29, wherein the method results in a decrease in IgG1 levels in the subject.

31. The method of claim 30, wherein the IgG1 levels are IgG1 protein levels or IgG1 mRNA
levels.

32. The method of any one of claim 1 to 31, wherein the method results in a decrease in IgE
levels in the subject.

33. The method of claim 32, wherein the IgE levels are IgE protein levels or IgE mRNA
levels.

34. The method of any one of claim 1 to 33, wherein the method results in a decrease in IgA
levels in the subject.

35. The method of claim 34, wherein the IgA levels are IgA protein levels or IgA mRNA
levels.

36. The method of any one of claims 1 to 35, wherein the Prevotella bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella muhtformis, Prevotella nigrescens, Prevotella orahs, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella muhisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, and/or Prevotella verorahs.

37. The method of claim 36, wherein the Prevotella bacteria are Prevotella histicola.

38. The method of any one of claims 1 to 37, wherein the Prevotella bacteria are a strain comprising at least 95% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).

39. The method of claim 38, wherein the Prevotella bacteria are a strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).

40. The method of claims 39, wherein the Prevotella bacteria are Prevotella Strain B 50329 (NRRL accession number B 50329).

41. The method of any one of claims 1 to 40, wherein the Prevotella bacteria are a strain of Prevotella bacteria comprising one or more proteins listed in Table 1.

42. The method of any one of claims 1 to 41, wherein the Prevotella bacteria are a strain of Prevotella substantially free of a protein listed in Table 2.

43. The method of any one of claims 1 to 42, wherein the pharmaceutical composition comprises live, killed, or attenuated bacteria.

44. The method of any one of claims 1 to 42, wherein the Prevotella bacteria are gamma irradiated, UV irradiated, heat inactivated, acid treated and/or oxygen sparged.

45. The method of claim 44, wherein the Prevotella bacteria are heat inactivated at 50 C for two hours or at 90 C for two hours.

46. The method of claim 44, wherein the Prevotella bacteria are oxygen sparged at 0.1 vvm for two hours.

47. The method of any one of claims 1 to 46, wherein the Prevotella bacteria are lyophilized Prevotella bacteria.

48. The method of claim 47, wherein the composition further comprises a pharmaceutically acceptable excipient.

49. The method of any one of claims 1 to 48, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species.

50. The method of any one of claims 1 to 48, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain.

51. The method of any one of claims 1 to 48, wherein the Prevotella bacteria in the pharmaceutical composition are from different species.

52. The method of any one of claims 1 to 49, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strains.

53. The method of any one of claims 1 to 52, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent.

54. The method of claim 53, wherein the additional therapeutic agent is an anti-inflammatory agent.

55. The method of any one of claims 1 to 54, wherein the pharmaceutical composition is formulated as a solid dose form.

56. The method of claim 55, wherein the solid dose form is a tablet, a minitablet, a capsule, a pill, or a powder, or a combination thereof.

57. The method of claim 55 or 56, wherein the solid dose form further comprises a pharmaceutically acceptable excipient.

58. The method of any one of claims 55 to 57, wherein the solid dose form comprises an enteric coating.

59. The method of any one of claims 55 to 58, wherein the solid dose form is formulated for oral administration.

60. The method of any one of claims 1 to 54, wherein the pharmaceutical composition is formulated as a suspension.

61. The method of claim 60, wherein the suspension is formulated for oral administration.

62. The method of claim 60 or 61, wherein the suspension comprises PBS, and optionally, sucrose or glucose.

63. The method of claim 60, wherein the suspension is formulated for intravenous administration.

64. The method of claim 60, wherein the suspension is formulated for intraperitoneal administration.

65. The method of claim 63 or 64, wherein the suspension comprises PBS.

66. The method of claim 60, wherein the pharmaceutical composition is administered intravenously.

67. The method of claim 60, wherein the pharmaceutical composition is administered by injection, e.g., subcutaneous, intradermal, or intraperitoneal injection.

68. The method of any one of claims 60 to 67, wherein the suspension further comprises a pharmaceutically acceptable excipient.

69. The method of any one of claims 60 to 68, wherein the suspension further comprises a buffer.

70. The method of claim 69, wherein the buffer is PBS.

71. The method of any one of claims 1 to 70, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

72. The method of claim 71, wherein the one or more additional therapeutic agent is one or more anti-inflammatory agent.

73. The method of any one of claims 1 to 62 or 68 to 72, wherein the pharmaceutical composition is administered orally.

74. The method of any one of claims 1 to 73, wherein the pharmaceutical composition comprises about 5 mg to about 900 mg total protein as determined by Bradford assay or BCA
assay.

75. The method of any one of claims 1 to 74, wherein the pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by Bradford assay or BCA assay.

76. The method of any one of claims 1 to 75, further comprising administering to the subject an additional therapeutic agent.

77. The method of claim 76, wherein the additional therapeutic agent is an anti-inflammatory agent.

78. The method of claim 76, wherein the additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukatriene receptor antagonist, an antibody, or a combination thereof.

79. The method of claim 76 or 77, wherein the pharmaceutical composition comprises the additional therapeutic agent.

80. The method of claim 76, wherein the additional therapeutic agent is an antibiotic agent.

81. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria for use in treating or preventing a TH2-mediated condition in a subject.

82. The pharmaceutical composition of claim 81, wherein the subject is a human subject.

83. The pharmaceutical composition of claim 81 or claim 82, wherien at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial-derived content of the pharmaceutical composition is derived from Prevotella bacteria.

84. The pharmaceutical composition of any one of claims 81 to 83, wherein the pharmaceutical composition treats the TH2-mediated condition.

85. The pharmaceutical composition of any one of claims 81 to 84, wherein the TH2-mediated condition is asthma, atopic dermatitis, an eosinophilic disease, and/or an allergy.

86. The pharmaceutical composition of claim 85, wherein TH2-mediated condition is an allergy, and the allergy is a food allergy, seasonal allergic rhinitis, and/or a pet allergy.

87. The pharmaceutical composition of claim 85, wherein the TH2-mediated condition is atopic dermatitis.

88. The pharmaceutical composition of claim 85, wherein the TH2-mediated condition is a food allergy.

89. The pharmaceutical composition of claim 88, wherein the food allergy is a peanut, cow's milk, hen egg, fish, crustacean shellfish, tree nut, wheat, or soy allergy.

90. The pharmaceutical composition of claim 88, wherein the food allergy is a peanut allergy.

91. The pharmaceutical composition of claim 88, wherein food allergy is an allergy to a food antigen.

92. The pharmaceutical composition of claim 91, wherein the food antigen is a peanut antigen, a cow's milk antigen, a hen egg antigen, a fish antigen, a crustacean shellfish antigen, a tree nut antigen, a wheat antigen, or a soy antigen.

93. The pharmaceutical composition claim 91, wherein the food antigen is a peanut antigen.

94. The pharmaceutical composition of any one of claim 81 to 93, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-4 levels in the subject.

95. The pharmaceutical composition of claim 94, wherein the IL-4 levels are IL-4 protein levels or IL-4 mRNA levels.

96. The pharmaceutical composition of any one of claim 81 to 95, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-5 levels in the subject.

97. The pharmaceutical composition of claim 96, wherein the IL-5 levels are IL-5 protein levels or IL-5 mRNA levels.

98. The pharmaceutical composition of any one of claim 81 to 97, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-13 levels in the subject.

99. The pharmaceutical composition of claim 98, wherein the IL-13 levels are IL-13 protein levels or IL-13 mRNA levels.

100. The pharmaceutical composition of any one of claim 81 to 99, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-19 levels in the subject.

101. The pharmaceutical composition of claim 100, wherein the IL-19 levels are IL-19 protein levels or IL-19 mRNA levels.

102. The pharmaceutical composition of any one of claim 81 to 101, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-21 levels in the subject.

103. The pharmaceutical composition of claim 102, wherein the IL-21 levels are IL-21 protein levels or IL-21 mRNA levels.

104. The pharmaceutical composition of any one of claim 81 to 103, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-31 levels in the subject.

105. The pharmaceutical composition of claim 104, wherein the IL-31 levels are IL-31 protein levels or IL-31 mRNA levels.

106. The pharmaceutical composition of any one of claim 81 to 105, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-33 levels in the subject.

107. The pharmaceutical composition of claim 106, wherein the IL-33 levels are IL-33 protein levels or IL-4 mRNA levels.

108. The pharmaceutical composition of any one of claim 81 to 107, wherein administration of the pharmaceutical composition results in a decrease in Thymic Stromal Lymphopoietin (TSLP) levels in the subject.

109. The pharmaceutical composition of claim 108, wherein the TSLP levels are TSLP protein levels or TSLP mRNA levels.

110. The pharmaceutical composition of any one of claim 81 to 109, wherein administration of the pharmaceutical composition results in a decrease in IgG1 levels in the subject.

111. The pharmaceutical composition of claim 110, wherein the IgG1 levels are IgG1 protein levels or IgG1 mRNA levels.

112. The pharmaceutical composition of any one of claim 81 to 111, wherein administration of the pharmaceutical composition results in a decrease in IgE levels in the subject.

113. The pharmaceutical composition of claim 112, wherein the IgE levels are IgE protein levels or IgE mRNA levels.

114. The pharmaceutical composition of any one of claim 81 to 113, wherein administration of the pharmaceutical composition results in a decrease in IgA levels in the subject.

115. The pharmaceutical composition of claim 114, wherein the IgA levels are IgA protein levels or IgA mRNA levels.

116. The pharmaceutical composition of any one of claims 81 to 115, wherein the Prevotella bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccahs, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella muhiformis, Prevotella nigrescens, Prevotella orahs, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella muhisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, and/or Prevotella verorahs.

117. The pharmaceutical composition of claim 116, wherein the Prevotella bacteria are Prevotella histicola.

118. The pharmaceutical composition of any one of claims 81 to 117, wherein the Prevotella bacteria are a strain comprising at least 95% genomic, 16S and/or CRISPR
sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).

119. The pharmaceutical composition of claim 118, wherein the Prevotella bacteria are a strain comprising at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).

120. The pharmaceutical composition of claims 119, wherein the Prevotella bacteria are Prevotella Strain B 50329 (NRRL accession number B 50329).

121. The pharmaceutical composition of any one of claims 81 to 120, wherein the Prevotella bacteria are a strain of Prevotella bacteria comprising one or more proteins listed in Table 1.

122. The pharmaceutical composition of any one of claims 81 to 121, wherein the Prevotella bacteria are a strain of Prevotella substantially free of a protein listed in Table 2.

123. The pharmaceutical composition of any one of claims 81 to 122, wherein the pharmaceutical composition comprises live, killed, or attenuated bacteria.

124. The pharmaceutical composition of any one of claims 81 to 122, wherein the Prevotella bacteria are gamma irradiated, UV irradiated, heat inactivated, acid treated and/or oxygen sparged.

125. The pharmaceutical composition of claim 124, wherein the Prevotella bacteria are heat inactivated at 50 C for two hours or at 90 C for two hours.

126. The pharmaceutical composition of claim 124, wherein the Prevotella bacteria are oxygen sparged at 0.1 vvm for two hours.

127. The pharmaceutical composition of any one of claims 81 to 126, wherein the Prevotella bacteria are lyophilized Prevotella bacteria.

128. The pharmaceutical composition of claim 127, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

129. The pharmaceutical composition of any one of claims 81 to 128, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species.

130. The pharmaceutical composition of any one of claims 81 to 128, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain.

131. The pharmaceutical composition of any one of claims 81 to 128, wherein the Prevotella bacteria in the pharmaceutical composition are from different species.

132. The pharmaceutical composition of any one of claims 81 to 129, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strains.

133. The pharmaceutical composition of any one of claims 81 to 132, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent.

134. The pharmaceutical composition of claim 133, wherein the additional therapeutic agent is an anti-inflammatory agent.

135. The pharmaceutical composition of any one of claims 81 to 134, wherein the pharmaceutical composition is formulated as a solid dose form.

136. The pharmaceutical composition of claim 135, wherein the solid dose form is a tablet, a minitablet, a capsule, a pill, or a powder, or a combination thereof.

137. The pharmaceutical composition of claim 135 or 136, wherein the solid dose form further comprises a pharmaceutically acceptable excipient.

138. The pharmaceutical composition of any one of claims 135 to 137, wherein the solid dose form comprises an enteric coating.

139. The pharmaceutical composition of any one of claims 135 to 138, wherein the solid dose form is formulated for oral administration.

140. The pharmaceutical composition of any one of claims 81 to 134, wherein the pharmaceutical composition is formulated as a suspension.

141. The pharmaceutical composition of claim 140, wherein the suspension is formulated for oral administration.

142. The pharmaceutical composition of claim 140 or 141, wherein the suspension comprises PBS, and optionally, sucrose or glucose.

143. The pharmaceutical composition of claim 140, wherein the suspension is formulated for intravenous administration.

144. The pharmaceutical composition of claim 140, wherein the suspension is formulated for intraperitoneal administration.

145. The pharmaceutical composition of claim 143 or 144, wherein the suspension comprises PBS.

146. The pharmaceutical composition of claim 140, wherein the pharmaceutical composition is administered intravenously.

147. The pharmaceutical composition of claim 140, wherein the pharmaceutical composition is administered by injection, e.g., subcutaneous, intradermal, or intraperitoneal injection.

148. The pharmaceutical composition of any one of claims 140 to 147, wherein the suspension further comprises a pharmaceutically acceptable excipient.

149. The pharmaceutical composition of any one of claims 140 to 148, wherein the suspension further comprises a buffer.

150. The pharmaceutical composition of claim 149, wherein the buffer is PBS.

151. The pharmaceutical composition of any one of claims 81 to 150, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

152. The pharmaceutical composition of claim 151, wherein the one or more additional therapeutic agent is one or more anti-inflammatory agent.

153. The pharmaceutical composition of any one of claims 81 to 142 or 148 to 152, wherein the pharmaceutical composition is administered orally.

154. The pharmaceutical composition of any one of claims 81 to 153, wherein the pharmaceutical composition comprises about 5 mg to about 900 mg total protein as determined by Bradford assay or BCA assay.

155. The pharmaceutical composition of any one of claims 81 to 154, wherein the pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by Bradford assay or BCA assay.

156. The pharmaceutical composition of any one of claims 81 to 155, wherein the pharmaceutical composition is administered to the subject with an additional therapeutic agent.

157. The pharmaceutical composition of claim 156, wherein the additional therapeutic agent is an anti-inflammatory agent.

158. The pharmaceutical composition of claim 156, wherein the additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukatriene receptor antagonist, an antibody, or a combination thereof.

159. The pharmaceutical composition of claim 156 or 157, wherein the pharmaceutical composition comprises the additional therapeutic agent.

160. The pharmaceutical composition of claim 156, wherein the additional therapeutic agent is an antibiotic agent.

161. Use of a pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria for the manufacture of a medicament for treating or preventing a TH2-mediated condition in a subject.

162. The use of claim 161, wherein the subject is a human subject.

163. The use of claim 161 or claim 162, wherien at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial-derived content of the pharmaceutical composition is derived from Prevotella bacteria.

164. The use of any one of claims 161 to 163, wherein the use treats the TH2-mediated condition.

165. The use of any one of claims 161 to 164, wherein the TH2-mediated condition is asthma, atopic dermatitis, an eosinophilic disease, and/or an allergy.

166. The use of claim 165, wherein TH2-mediated condition is an allergy, and the allergy is a food allergy, seasonal allergic rhinitis, and/or a pet allergy.

167. The use of claim 165, wherein the TH2-mediated condition is atopic dermatitis.

168. The use of claim 165, wherein the TH2-mediated condition is a food allergy.

169. The use of claim 168, wherein the food allergy is a peanut, cow's milk, hen egg, fish, crustacean shellfish, tree nut, wheat, or soy allergy.

170. The use of claim 168, wherein the food allergy is a peanut allergy.

171. The use of claim 168, wherein food allergy is an allergy to a food antigen.

172. The use of claim 171, wherein the food antigen is a peanut antigen, a cow's milk antigen, a hen egg antigen, a fish antigen, a crustacean shellfish antigen, a tree nut antigen, a wheat antigen, or a soy antigen.

173. The use claim 171, wherein the food antigen is a peanut antigen.

174. The use of any one of claim 161 to 173, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-4 levels in the subject.

175. The use of claim 174, wherein the IL-4 levels are IL-4 protein levels or IL-4 mRNA
levels.

176. The use of any one of claim 161 to 175, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-5 levels in the subject.

177. The use of claim 176, wherein the IL-5 levels are IL-5 protein levels or IL-5 mRNA
levels.

178. The use of any one of claim 161 to 177, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-13 levels in the subject.

179. The use of claim 178, wherein the IL-13 levels are IL-13 protein levels or IL-13 mRNA
levels.

180. The use of any one of claim 161 to 179, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-19 levels in the subject.

181. The use of claim 180, wherein the IL-19 levels are IL-19 protein levels or IL-19 mRNA
levels.

182. The use of any one of claim 161 to 181, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-21 levels in the subject.

183. The use of claim 182, wherein the IL-21 levels are IL-21 protein levels or IL-21 mRNA
levels.

184. The use of any one of claim 161 to 183, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-31 levels in the subject.

185. The use of claim 184, wherein the IL-31 levels are IL-31 protein levels or IL-31 mRNA
levels.

186. The use of any one of claim 161 to 185, wherein administration of the pharmaceutical composition results in a decrease in interleukin (IL)-33 levels in the subject.

187. The use of claim 186, wherein the IL-33 levels are IL-33 protein levels or IL-4 mRNA
levels.

188. The use of any one of claim 161 to 187, wherein administration of the pharmaceutical composition results in a decrease in Thymic Stromal Lymphopoietin (TSLP) levels in the subj ect.

189. The use of claim 188, wherein the TSLP levels are TSLP protein levels or TSLP mRNA
levels.

190. The use of any one of claim 161 to 189, wherein administration of the pharmaceutical composition results in a decrease in IgG1 levels in the subject.

191. The use of claim 190, wherein the IgG1 levels are IgG1 protein levels or IgG1 mRNA
levels.

192. The use of any one of claim 161 to 191, wherein administration of the pharmaceutical composition results in a decrease in IgE levels in the subject.

193. The use of claim 192, wherein the IgE levels are IgE protein levels or IgE mRNA levels.

194. The use of any one of claim 161 to 193, wherein administration of the pharmaceutical composition results in a decrease in IgA levels in the subject.

195. The use of claim 194, wherein the IgA levels are IgA protein levels or IgA mRNA levels.

196. The use of any one of claims 161 to 195, wherein the Prevotella bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccahs, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella muhtformis, Prevotella nigrescens, Prevotella orahs, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella muhisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, and/or Prevotella verorahs.

197. The use of claim 196, wherein the Prevotella bacteria are Prevotella histicola.

198. The use of any one of claims 161 to 197, wherein the Prevotella bacteria are a strain comprising at least 95% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).

199. The use of claim 198, wherein the Prevotella bacteria are a strain comprising at least 99%
genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).

200. The use of claims 199, wherein the Prevotella bacteria are Prevotella Strain B 50329 (NRRL accession number B 50329).

201. The use of any one of claims 161 to 200, wherein the Prevotella bacteria are a strain of Prevotella bacteria comprising one or more proteins listed in Table 1.

202. The use of any one of claims 161 to 201, wherein the Prevotella bacteria are a strain of Prevotella substantially free of a protein listed in Table 2.

203. The use of any one of claims 161 to 202, wherein the pharmaceutical composition comprises live, killed, or attenuated bacteria.

204. The use of any one of claims 161 to 202, wherein the Prevotella bacteria are gamma irradiated, UV irradiated, heat inactivated, acid treated and/or oxygen sparged.

205. The use of claim 204, wherein the Prevotella bacteria are heat inactivated at 50 C for two hours or at 90 C for two hours.

206. The use of claim 204, wherein the Prevotella bacteria are oxygen sparged at 0.1 vvm for two hours.

207. The use of any one of claims 161 to 206, wherein the Prevotella bacteria are lyophilized Prevotella bacteria.

208. The use of claim 207, wherein the composition further comprises a pharmaceutically acceptable excipient.

209. The use of any one of claims 161 to 208, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species.

210. The use of any one of claims 161 to 208, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain.

211. The use of any one of claims 161 to 208, wherein the Prevotella bacteria in the pharmaceutical composition are from different species.

212. The use of any one of claims 161 to 209, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strains.

213. The use of any one of claims 161 to 212, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent.

214. The use of claim 213, wherein the additional therapeutic agent is an anti-inflammatory agent.

215. The use of any one of claims 161 to 214, wherein the pharmaceutical composition is formulated as a solid dose form.

216. The use of claim 215, wherein the solid dose form is a tablet, a minitablet, a capsule, a pill, or a powder, or a combination thereof.

217. The use of claim 215 or 216, wherein the solid dose form further comprises a pharmaceutically acceptable excipient.

218. The use of any one of claims 215 to 217, wherein the solid dose form comprises an enteric coating.

219. The use of any one of claims 215 to 218, wherein the solid dose form is formulated for oral administration.

220. The use of any one of claims 161 to 214, wherein the pharmaceutical composition is formulated as a suspension.

221. The use of claim 220, wherein the suspension is formulated for oral administration.

222. The use of claim 220 or 221, wherein the suspension comprises PBS, and optionally, sucrose or glucose.

223. The use of claim 220, wherein the suspension is formulated for intravenous administration.

224. The use of claim 220, wherein the suspension is formulated for intraperitoneal administration.

225. The use of claim 223 or 224, wherein the suspension comprises PBS.

226. The use of claim 220, wherein the pharmaceutical composition is administered intravenously.

227. The use of claim 220, wherein the pharmaceutical composition is administered by injection, e.g., subcutaneous, intradermal, or intraperitoneal injection.

228. The use of any one of claims 220 to 227, wherein the suspension further comprises a pharmaceutically acceptable excipient.

229. The use of any one of claims 220 to 228, wherein the suspension further comprises a buffer.

230. The use of claim 229, wherein the buffer is PBS.

231. The use of any one of claims 161 to 230, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

232. The use of claim 231, wherein the one or more additional therapeutic agent is one or more anti-inflammatory agent.

233. The use of any one of claims 161 to 222 or 228 to 232, wherein the pharmaceutical composition is administered orally.

234. The use of any one of claims 161 to 233, wherein the pharmaceutical composition comprises about 5 mg to about 900 mg total protein as determined by Bradford assay or BCA
assay.

235. The use of any one of claims 161 to 234, wherein the pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by Bradford assay or BCA assay.