JP2022536861A - Compositions and methods of treating TH2-mediated conditions using Prevotella - Google Patents

Abstract

Provided herein are compositions relating to Prevotella bacteria that may be useful as therapeutic agents, e.g., therapeutic agents for the treatment of TH2-mediated conditions such as atopic dermatitis and/or food allergies, and The method. [Selection figure] None

Description

RELATED APPLICATIONS This application is the subject of U.S. Provisional Application No. 62/864,886, filed June 21, 2019, and U.S. Provisional Application No. 62/910,920, filed October 4, 2019. Priority to the specification and benefit of their filing dates are claimed, both of which are hereby incorporated by reference in their entireties.

Helper T (T _H ) cells (also called CD4 ⁺ T cells) influence the activity of other immune cells such as B cells, other T cells, eosinophils, basophils, mast cells, and macrophages. regulates the adaptive immune response by secreting cytokines that exert

When naive T _H cells are activated, they differentiate into one of a variety of T _H cell subsets, each of which is involved in modulating one aspect of the immune response by secreting a specific set of cytokines. do. For example, T _H 1 cells secrete IFN-γ and are involved in enhancing cell-mediated immune responses against viruses and intracellular bacteria. T _H 2 cells, on the other hand, secrete IL-4, IL-5, IL-9, IL-10, IL-13, and IL-25, and are particularly useful against extracellular parasites such as helminths. Involved in enhancing the immune response. T _H 17 cells secrete IL-17 and mediate inflammatory responses, such as those against fungi (among other pathogens).

Which T _H cells a T _H subset differentiates into upon activation is determined in part by the presence of certain polarizing cytokines. For example, if naive T _H cells were activated in the presence of IFN-γ, they would likely differentiate into T _H 1 cells. On the other hand, if naive T _H cells were activated in the presence of IL-4, they would likely differentiate into T _H 2 cells. Thus, secretion of IFN-γ by activated T _H 1 cells can polarize other T H cells into the T _H 1 subset, while secretion of IL-4 by activated T _H 2 cells can lead to Other TH cells can be polarized into the T _H 2 subset. Through this chain effect, T _H cell differentiation can have a broad impact on a person's overall immune response. Indeed, many diseases and disorders are associated with T _H2 immune responses, including but not limited to: allergies (e.g., food allergies, insect-induced allergies, insect-induced allergy), drug allergy, or allergic rhinitis), asthma, and atopic dermatitis.

Therefore, novel compositions for stimulating T _H 1 immune responses and/or _{inhibiting T H 2 immune responses to treat such T H 2} -mediated conditions. An article and method are needed.

As disclosed herein, pharmaceutical compositions comprising bacteria of the genus Prevotella have therapeutic efficacy and are used for the treatment of one or more T _H2 -mediated conditions and/or It is useful for prophylaxis (eg, treatment, prevention, or both treatment and prevention). Such T _H2 -mediated conditions include, but are not limited to: allergic rhinitis, asthma, atopic dermatitis, urticaria, angioedema, allergies (e.g., food allergies, insect-induced allergies). , drug allergy), anaphylaxis, and eosinophilia.

In some aspects, provided herein are methods of treating and/or preventing a T _H2 -mediated condition in a subject. In certain embodiments, the method comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising bacteria of the genus Prevotella.

In certain aspects, provided herein are pharmaceutical compositions comprising bacteria of the genus Prevotella that are useful for the treatment or prevention of one or more T _H2 -mediated conditions. . Thus, in certain aspects, provided herein are pharmaceutical compositions comprising bacteria of the genus Prevotella for use in treating or preventing a T _H2 -mediated condition.

In certain aspects, provided herein is the use of a pharmaceutical composition comprising a bacterium of the genus Prevotella for the preparation of a medicament for the treatment or prevention of a T _H2 -mediated condition. is.

In certain embodiments, the T _H2 -mediated condition is allergy, atopic dermatitis, asthma, urticaria, angioedema, anaphylaxis, eosinophilia, or a combination thereof.

In some embodiments, the T _H2 -mediated condition is allergy. In certain embodiments, the allergy is allergic rhinitis, food allergy, insect-induced allergy, or drug allergy. In some embodiments, the allergy is food allergy. In some embodiments, the food allergies may include allergies to eggs, milk, peanuts, tree nuts (eg, walnuts), fish, shellfish, wheat, soybeans, or combinations thereof.

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

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 % are Prevotella bacteria or biological material derived from Prevotella bacteria.

In certain embodiments of any one of the aspects disclosed herein, the bacterium of the genus Prevotella comprises at least one protein having an amino acid sequence selected from SEQ ID NOs: 1-41 including. Additionally or alternatively, in some embodiments, the bacterium of the genus Prevotella has at least one or more of each protein having an amino acid sequence selected from SEQ ID NOS: 42-69. Not substantially included.

In some embodiments of any one of the aspects disclosed herein, Prevotella bacteria include bacteria of the following species: Prevotella albensis, Prevotella aminii (Prevotella amnii), Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella bukkale (Prevotella buccaceae) Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｌｉｓ）、プレボテラ・コプリ（Ｐｒｅｖｏｔｅｌｌａ ｃｏｐｒｉ）、プレボテラ・デンタリス（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｌｉｓ）、プレボテラ・デンティコーラ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔｉｃｏｌａ）、プレボテラ・ディシエンス（Ｐｒｅｖｏｔｅｌｌａ ｄｉｓｉｅｎｓ）、プレボテラ・ヒスチコーラ（Ｐｒｅｖｏｔｅｌｌａ ｈｉｓｔｉｃｏｌａ）、プレボテラ・インターメディア（Ｐｒｅｖｏｔｅｌｌａ ｉｎｔｅｒｍｅｄｉａ）、プレボテラ・マクローサ（Ｐｒｅｖｏｔｅｌｌａ ｍａｃｕｌｏｓａ）、プレボテラ・マルシイ（Ｐｒｅｖｏｔｅｌｌａ ｍａｒｓｈｉｉ）、プレボテラ・メラニノジェニカ（Ｐｒｅｖｏｔｅｌｌａ ｍｅｌａｎｉｎｏｇｅｎｉｃａ）、プレボテラ・マイカンス（Ｐｒｅｖｏｔｅｌｌａ ｍｉｃａｎｓ）、プレボテラ・マルチフォルミス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｆｏｒｍｉｓ）、プレボテラ・ニグレッセンス（Ｐｒｅｖｏｔｅｌｌａ ｎｉｇｒｅｓｃｅｎｓ）、プレボテラ・オラリス（Ｐｒｅｖｏｔｅｌｌａ ｏｒａｌｉｓ）、プレボテラ・オリス（Ｐｒｅｖｏｔｅｌｌａ ｏｒｉｓ）、プレボテラ・オウロラム（Ｐｒｅｖｏｔｅｌｌａ ｏｕｌｏｒｕｍ）、プレボテラ・パレンス（Ｐｒｅｖｏｔｅｌｌａ ｐａｌｌｅｎｓ）、プレボテラ・サリバーエ（Ｐｒｅｖｏｔｅｌｌａ ｓａｌｉｖａｅ）、プレボテラ・ステルコレア（Ｐｒｅｖｏｔｅｌｌａ ｓｔｅｒｃｏｒｅａ） , Prevotella tannerae, Prevotella timoneンシス（Ｐｒｅｖｏｔｅｌｌａ ｔｉｍｏｎｅｎｓｉｓ）、プレボテラ・ジェジュニ（Ｐｒｅｖｏｔｅｌｌａ ｊｅｊｕｎｉ）、プレボテラ・オーランティアカ（Ｐｒｅｖｏｔｅｌｌａ ａｕｒａｎｔｉａｃａ）、プレボテラ・バーロニアエ（Ｐｒｅｖｏｔｅｌｌａ ｂａｒｏｎｉａｅ）、プレボテラ・コロランス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｌｏｒａｎｓ）、プレボテラ・コルポリス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｒｐｏｒｉｓ）、プレボテラ・デンタシニ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｓｉｎｉ）、プレボテラ・エノエカ（Ｐｒｅｖｏｔｅｌｌａ ｅｎｏｅｃａ）、プレボテラ・ファルセニイ（Ｐｒｅｖｏｔｅｌｌａ ｆａｌｓｅｎｉｉ）、プレボテラ・フスカ（Ｐｒｅｖｏｔｅｌｌａ ｆｕｓｃａ）、プレボテラ・ヘパリノリティカ（Ｐｒｅｖｏｔｅｌｌａ ｈｅｐａｒｉｎｏｌｙｔｉｃａ）、プレボテラ・ロエッシェイイ（Ｐｒｅｖｏｔｅｌｌａ ｌｏｅｓｃｈｅｉｉ）、プレボテラ・マルチサッカリボラックス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｓａｃｃｈａｒｉｖｏｒａｘ）、プレボテラ・ナンセイエンシス（Ｐｒｅｖｏｔｅｌｌａ ｎａｎｃｅｉｅｎｓｉｓ）、プレボテラ・オリザエ（Ｐｒｅｖｏｔｅｌｌａ ｏｒｙｚａｅ）、プレボテラ・パルディビエンス（Ｐｒｅｖｏｔｅｌｌａ ｐａｌｕｄｉｖｉｖｅｎｓ）、プレボテラ・プレウリチディス（Ｐｒｅｖｏｔｅｌｌａ ｐｌｅｕｒｉｔｉｄｉｓ）、プレボテラ・ルミニコーラ（Ｐｒｅｖｏｔｅｌｌａ ｒｕｍｉｎｉｃｏｌａ）、プレボテラ・サッカロリティカ（Ｐｒｅｖｏｔｅｌｌａ ｓａｃｃｈａｒｏｌｙｔｉｃａ）、プレボテラ・スコポス（Ｐｒｅｖｏｔｅｌｌａ ｓｃｏｐｏｓ）、プレボテラ・シャーヒイ（Ｐｒｅｖｏｔｅｌｌａ ｓｈａｈｉｉ）、プレボテラ・ズーグレオフォルマンス（Ｐｒｅｖｏｔｅｌｌａ ｚｏｏｇｌｅｏｆｏｒｍａｎｓ）、プレボテラ・ベロラリス（Ｐｒｅｖｏｔｅｌｌａ ｖｅｒｏｒａｌｉｓ）、又はこれらcombination. In some embodiments, bacteria of the genus Prevotella can include bacteria of the species Prevotella histicola.

In some embodiments, the Prevotella bacterium is 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 sequence identity, 16S ribosomal ribonucleic acid sequence identity, and/or Or strains with regularly spaced short palindromic repeat sequence identities can be included. In some embodiments, the Prevotella bacterium includes Prevotella histicola strain B 50329 (NRRL Accession: B 50329).

In some embodiments, the Prevotella bacterium is a strain of Prevotella bacterium comprising a protein listed in Table 1 and/or a gene encoding a protein listed in Table 1. In some embodiments, the Prevotella bacterium is free or substantially free of a protein listed in Table 2 and/or a gene encoding a protein listed in Table 2. ) is a bacterial strain. In some embodiments, the Prevotella histicola bacterium is a Prevotella histicola bacterium comprising a protein listed in Table 1 and/or a gene encoding a protein listed in Table 1 is a stock of In some embodiments, the Prevotella histicola bacterium is free or substantially free of the proteins listed in Table 2 and/or the genes encoding the proteins listed in Table 2 Prevotella histicola is a strain of the bacterium.

In certain embodiments, the pharmaceutical composition comprises a single species of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises multiple species of Prevotella bacteria (eg, 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 multiple strains of Prevotella bacteria (eg, 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 multiple strains of Prevotella histicola bacteria (eg, 2, 3, 4, 5 strains).

In some embodiments, the Prevotella bacterium of the pharmaceutical composition includes live, killed, or attenuated bacteria. In some embodiments, the Prevotella bacterium of the pharmaceutical composition includes live bacteria. In some embodiments, the pharmaceutical composition is gamma-irradiated, UV-irradiated, or heat-inactivated (e.g., 50° C. for 2 hours, 90° C. for 2 hours). , acid treated, or oxygen sparged (at 0.1 vvm for 2 hours). In certain embodiments, the Prevotella bacterium of the pharmaceutical composition includes lyophilized bacteria. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

In some embodiments of any one of the aspects disclosed herein, administration of the pharmaceutical composition to a subject causes the subject (e.g., the mesenteric or cervical lymph nodes) to ) and/or the _{level of mRNA encoding the T H2 protein} may be reduced. By way of example, in certain embodiments, upon administration of the pharmaceutical composition, the level of T _H2 protein and/or mRNA encoding T _H2 protein is greater than T H2 protein and/or mRNA encoding T _H2 protein prior to administration of the pharmaceutical composition. /or reduced in the subject when compared to the level of mRNA encoding the T _H 2 protein. In certain embodiments, the T _H 2 protein is interleukin-4 (IL-4), interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-33, thymus thymic stromal lymphopoietin, immunoglobulin G1, immunoglobulin E, immunoglobulin A, or combinations thereof. In certain embodiments, the T _H 2 protein is IL-4, IL-13, IL-5, IL-31, IL-33, or a combination thereof. In certain embodiments, the T _H 2 protein is IL-13, IL-5, IL-31, or a combination thereof. In certain embodiments, the T _H 2 protein is IL-13. In certain embodiments, the T _H 2 protein is IL-31. In certain embodiments, the T _H 2-mRA is Il4, Il5, IL31, Il33, Tslp, Ccl9, Ccr4, or a combination thereof. In certain embodiments, the T _H 2-mRA is 114, 115, 1133, 1117a, 111b, Tslp, or a combination thereof. In certain embodiments, the T _H 2-mRA is Il4, Il5, Tslp, Ccr4, Il19, or a combination thereof. In certain embodiments, the T _H 2-mRA is Il5, Il31, and Ccr4, or a combination thereof. In certain embodiments, the T _H 2-mRA is Il5.

In some embodiments of one of the aspects disclosed herein, administration of the pharmaceutical composition to a subject results in mast cell-associated proteins and/or mast cells in the subject (eg, the jejunum thereof). A decrease in the level of mRNA encoding the relevant protein can be caused. In certain embodiments, the mast cell mRNA is Mcpt1. By way of example, in certain embodiments, upon administration of the pharmaceutical composition, the level of mast cell-associated protein and/or mRNA encoding mast cell-associated protein is greater than that of mast cell-associated protein and/or mast cell-associated protein prior to administration of the pharmaceutical composition and /or reduced in the subject when compared to the level of mRNA encoding mast cell-associated protein.

In some embodiments of any one of the aspects disclosed herein, administration of the pharmaceutical composition to the subject results in IL in the subject (e.g., the spleen or mesenteric lymph nodes thereof). A level increase of -10 can be caused. By way of example, in certain embodiments, upon administration of the pharmaceutical composition, the level of IL-10 and/or mRNA encoding IL-10 is greater than IL-10 and/or IL-10 prior to administration of the pharmaceutical composition. Elevated in subjects (eg, their spleen or mesenteric lymph nodes) when compared to levels of mRNA encoding -10.

In some embodiments of any one of the aspects disclosed herein, the subject is administered an additional therapeutic agent. In some embodiments, this additional agent is an anti-inflammatory agent. In certain embodiments, the additional therapeutic agent is a corticosteroid, antihistamine, mast cell stabilizer, decongestant, leukotriene receptor antagonist, antibody, or combination thereof. For example, the additional therapeutic agent can be: acrivastine, albuterol, alimemazine, ANB020, and benralizumab, antazoline, AS1517499, AS1810722, astemizole, azathioprine, AZD1981, azelastine, beclomethasone, bepotastine, betamethasone, BI671800, bilastine, bromazine. , brompheniramine, budesonide, budesonide-formoterol, carbinoxamine, cetirizine, chlorcyclidine, chloropyramine, chlorphenamine, ciclesonide, cyclosporine, cimetidine, clemastine, cortisone, chrysabolol, cromolyn, cyclidine, cyproheptadine, CYT003. , dapsone, desloratadine, dexamethasone, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimethindene, diphenhydramine, doxylamine, dupilumab, ebastine, ephedrine, epinephrine, famotidine, fexofenadine, flunisolide, fluticasone, fluticasone furoate, fluticasone propionate, fluticasone-salmeterol, formoterol, formoterol-mometasone, GSK3772847, hydroxychloroquine, hydroxyzine, imiquimod, interferon gamma-1b, ipratropium, ketotifen, lebrikizumab, levalbuterol, levocabastine, levocetirizine, levomethamphetamine, loratadine, meclizine, meclofenam sodium phosphate, mepolizumab, mepyramine, methotrexate, methylprednisolone, mizolastine, MK-886, mometasone, montelukast, mycophenolate, mycophenolate mofetil, naphazoline, OC000459, olopatadine, omalizumab, orphenadrine, oxymetazoline, pheniramine, Phenylephrine, phenylpropanolamine, pimecrolimus, prednisolone, prednisone, promethazine, propylhexedrine, pseudoephedrine, kifenazine, ranitidine, resiquimod, reslizumab, RG6149/AMG282, rupatadine, salmeterol, SB010, sirolimus, sulfasalazine, synephrine, tacrolimus, terfenadine, tetrizodine , theoferline, thixocortol, tralokinumab, tramazoline, triamcinolone, triamcinolone acetonide, tripelennamine, triprolidine, vitamin D, xylometazoline, YM-341619, zafirlukast, zileuton, or combinations thereof. In certain embodiments, this additional therapeutic agent may be included as part of the pharmaceutical composition or may be separate.

In some embodiments, the pharmaceutical composition is administered orally, intravenously, subcutaneously, intradermally, or intraperitoneally. In some embodiments, the pharmaceutical composition is administered via oral administration.

In certain embodiments, the pharmaceutical composition has a total protein content of at least 5 mg (e.g., at least 10 mg, 20 mg, 30 mg, 40 mg, 50mg, 60mg, 70mg, 80mg, 90mg, 100mg, 110mg, 120mg, 130mg, 140mg, 150mg, 160mg, 170mg, 180mg, 190mg, 200mg, 210mg, 220mg, 230mg, 240mg, 250mg, 260mg, 270mg, 280mg, 290mg, 300mg 310mg 320mg 330mg 340mg 350mg 360mg 370mg 380mg 390mg 400mg 410mg 420mg 430mg 440mg 450mg 460mg 470mg 480mg 490mg 500mg 510mg 520mg 530mg 550mg,560mg,570mg,580mg,590mg,600mg,610mg,620mg,630mg,640mg,650mg,660mg,670mg,680mg,690mg,700mg,710mg,720mg,730mg,740mg,750mg,760mg,770mg,780mg,790mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, or 900 mg) and 900 mg or less (e.g., 890 mg, 880 mg, 870 mg, 860 mg, 850 mg, 840 mg, 830 mg, 820 mg, 810 mg) , 800mg, 790mg, 780mg, 770mg, 760mg, 750mg, 740mg, 730mg, 720mg, 710mg, 700mg, 690mg, 680mg, 670mg, 660mg, 650mg, 640mg, 630mg, 620mg, 610mg, 600mg, 590mg, 580mg, 570mg, 560mg , 550mg, 540mg, 530mg, 520mg, 510mg, 500mg, 490mg, 480mg, 470mg, 460mg, 450mg, 440mg, 430mg, 420mg, 410mg, 400mg, 390mg, 380mg, 370mg, 360mg, 350mg, 340mg, 330mg, 320mg, 310mg , 30 0 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 or less). In certain embodiments, the pharmaceutical composition has a total protein content of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg (e.g., as determined by the Bradford assay or as determined by the BSA assay). , 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 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, It can be about 890 mg, or about 900 mg.

In some embodiments, the pharmaceutical composition has a total bacterial load of Prevotella spp. 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., 19 mg or less, 18 mg or less, 17 mg or less, 16 mg or less, 15 mg or less, 14 mg or less, 13 mg or less, 12 mg or less, 11 mg or less, 10 mg or less, 9 mg or less, 8 mg or less, 7 mg or less, 6 mg or less, 5 mg) . In some embodiments, the pharmaceutical composition has a total amount of Prevotella spp. , 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.

In certain embodiments, the pharmaceutical composition (e.g., a total dose of the composition administered once or twice daily) contains at least 1 x 10 ¹⁰ total cells (e.g., at least 1 x 10 ¹⁰ of 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 of total cells, at least 7×10 ¹⁰ total cells, at least 8×10 ¹⁰ total cells, at least 9×10 ¹⁰ total cells, at least 1×10 ¹¹ total cells) of Prevotella bacteria including. In some embodiments, the pharmaceutical composition contains 9×10 ¹¹ total cells or less (e.g., 1×10 ¹⁰ total cells or less, 2×10 ¹⁰ total cells or less, 3×10 ¹⁰ total cells or less, ≤ 4 x 10 ¹⁰ total cells, ≤ 5 x 10 ¹⁰ total cells, ≤ 6 x 10 ¹⁰ total cells, ≤ 7 x 10 ¹⁰ total cells, 8 x 10 ¹⁰ ≤ 9 x 10 ¹⁰ total cells, ≤ 1 x 10 ¹¹ total cells, ≤ 2 x 10 ¹¹ total cells, ≤ 3 x 10 ¹¹ total cells, 4 x 10 ¹¹ 5×10 ¹¹ total cells or less, 6×10 ¹¹ total cells or less, 7×10 ¹¹ total cells or less, 8×10 ¹¹ or less total cells Prevotella Contains bacteria. In some embodiments, the pharmaceutical composition comprises about 6×10 ⁹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹⁰ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8×10 ¹⁰ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 3.2×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹⁰ to about 8×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹⁰ to about 1.6×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8×10 ¹⁰ to about 8×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹¹ to about 8×10 ¹¹ total cells of Prevotella bacteria.

In certain embodiments, provided herein are solid dosage forms comprising Prevotella bacteria. In some embodiments, the solid dosage form includes an enteric coating. In some embodiments, the solid dosage form is a capsule, eg, an enteric coated capsule. In some embodiments, each capsule contains about 8×10 ¹⁰ total cells of Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered to a subject, eg, once or twice daily. In some embodiments, one capsule (eg, containing about 8×10 ¹⁰ total cells) is administered to the subject, eg, once or twice daily. In some embodiments, two capsules (eg, each containing about 8×10 ¹⁰ total cells) are administered to the subject, eg, once or twice daily. In some embodiments, 4 capsules (eg, each containing about 8×10 ¹⁰ total cells) are administered to a subject, eg, once or twice daily. In some embodiments, 10 capsules (eg, each containing about 8×10 ¹⁰ total cells) are administered to a subject, eg, once or twice daily. In some embodiments, the Prevotella bacteria in the capsule are lyophilized (eg, in powder form).

In some embodiments, solid dosage forms include capsules. In some embodiments, the capsule is an enteric coated tablet. In some embodiments, the capsule comprises about 8×10 ¹⁰ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the capsule comprises about 1.6×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the capsule comprises about 3.2×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the capsule comprises about 8×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the Prevotella bacteria in the capsule are lyophilized (eg, in powder form).

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 tablets are 5 mm to 17 mm in diameter. In some embodiments, the tablet comprises about 8×10 ¹⁰ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the tablet comprises about 1.6×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the tablet comprises about 3.2×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the tablet comprises about 8×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

In some embodiments, the solid dosage form comprises mini-tablets. In some embodiments, the mini-tablets are enteric coated. In some embodiments, the mini-tablets are 1 mm to 4 mm in diameter. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) are 1 mm mini-tablets, 1.5 mm mini-tablets, 2 mm mini-tablets, 3 mm mini-tablets, or 4 mm mini-tablets. is. In some embodiments, the solid dosage form comprises mini-tablets comprising about 8×10 ¹⁰ total cells of Prevotella bacteria (eg, a total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets comprising about 1.6×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of multiple mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets comprising about 3.2×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of multiple mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets comprising about 8×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of a plurality of mini-tablets). In some embodiments, the Prevotella bacteria in the mini-tablets are lyophilized.

In some embodiments, mini-tablets (eg, enteric-coated mini-tablets) are in capsules. 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 (eg, is coated with) a non-enteric coating (eg, HPMC (hydroxylpropylmethylcellulose) or gelatin). In some embodiments, the capsule includes a non-enteric coating. In some embodiments, the capsule comprises hydroxylpropylmethylcellulose (HPMC). In some embodiments, the capsule contains gelatin. In some embodiments, a mini-tablet (e.g., an enteric-coated mini-tablet) comprising about 8 x 10 ¹¹ total cells of Prevotella bacteria is encased in a capsule, optionally comprising: The capsule contains HPMC.

In some embodiments, pharmaceutical compositions comprising Prevotella bacteria are prepared as powders (e.g., powders for resuspension or use in solid dosage forms (e.g., capsules)). or prepared as a solid dosage form (e.g., tablet, mini-tablet, capsule, pill, or powder), or as a combination of these forms (e.g., mini-tablet in capsule) . In certain embodiments, the powder may contain lyophilized bacteria.

In certain embodiments of any one of the aspects disclosed herein, the pharmaceutical composition is formulated as a solid dosage form. In some embodiments, the pharmaceutical composition has a dosage form selected from tablets, capsules, mini-tablets, powders, or combinations thereof. In some embodiments, the pharmaceutical composition is formulated as a suspension (eg, suspension in PBS). In some embodiments, pharmaceutical compositions formulated for oral, intravenous, subcutaneous, intradermal, and/or intraperitoneal administration. In some embodiments, pharmaceutical compositions are formulated for oral administration.

In some embodiments, the pharmaceutical composition comprises lyophilized Prevotella bacteria. In certain embodiments, the lyophilized Prevotella bacterium is formulated into a solid dosage form, e.g., a tablet, mini-tablet, capsule, pill, or powder. ing. In some embodiments, the lyophilized Prevotella bacteria are in capsules. In some embodiments, the lyophilized Prevotella bacteria are resuspended in a solution.

In certain embodiments, provided herein are methods of treating a subject having a T _H2 -mediated condition, wherein the subject is administered a pharmaceutical composition described herein. administering.

In certain embodiments, provided herein are methods of treating a subject with atopic dermatitis, comprising administering to the subject a pharmaceutical composition described herein It is a method that includes

In certain embodiments, provided herein are methods of treating a subject with food allergy, comprising administering to the subject a pharmaceutical composition described herein. It is a method of inclusion.

In some embodiments, the methods provided herein further comprise administering an antibiotic to the subject. In some embodiments, the method further comprises administering to the subject one or more other treatments for the condition. In some embodiments, the method further comprises administering another therapeutic bacterium.

Eight hours after FITC ear challenge in a contact hypersensitivity model using FITC, oral administration of Prevotella histicola significantly reduced ear swelling (normal one-way ANOVA; p<0.001 for P. histicola; p: 0.0031 for P. histicola). 10 is a series of graphs showing that Prevotella histicola treatment decreased gene expression of Il4, Il5, Il33, Il17a, Il1b, and Tslp in the ear. 10 is a series of graphs showing that Prevotella histicola treatment decreased gene expression of Il4, Il5, Il33, Il17a, Il1b, and Tslp in the ear. Eight hours after FITC ear challenge in a contact hypersensitivity model with FITC, oral administration of Prevotella histicola significantly reduced ear swelling (normal 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). Atopic dermatitis-associated food allergy model study design is shown. 10 is a graph showing that oral administration of Prevotella histicola significantly reduced ear inflammation in an atopic dermatitis-associated food allergy model using the ovalbumin (OVA) food allergen model (regular one-way ANOVA; p: 0.0009 for tofacitinib; p < 0.0001 for P. histicola; p: 0.0047 for strain B; strains of different genera, strain B being another strain of Prevotella histicola). Vehicle, tofacitinib, Prevotella histicola, or two other bacterial species (“strain A” and “strain B”) in an atopic dermatitis-associated food allergy model using the ovalbumin (OVA) food allergen ) is a pair of graphs showing IgG1 and IgE levels in mice treated with ) (strain A is a strain from a different genus than Prevotella and strain B is a different strain from Prevotella histicola). stocks). Vehicle, tofacitinib, Prevotella histicola, or two other bacterial species (“strain A” and “strain B”) in an atopic dermatitis-associated food allergy model using the ovalbumin (OVA) food allergen ) 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 the ovalbumin (OVA) food allergen ) 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 the ovalbumin (OVA) food allergen ) 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 the ovalbumin (OVA) food allergen ) 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 the ovalbumin (OVA) food allergen ) 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 the ovalbumin (OVA) food allergen ) is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered ). A mouse model study design to test an atopic dermatitis-associated food allergy model using ovalbumin (OVA) or CPE (complete peanut extract) as food allergens is shown. Oral administration of Prevotella histicola significantly reduced ear inflammation in both an atopic dermatitis-associated food allergy model using OVA and an atopic dermatitis-associated food allergy model using peanut allergen (CPE) (Normal one-way ANOVA; p: <0.0001 for tofacitinib; p: 0.0024 for anti-IL-4; p: 0.0163 for strain A; p. p<0.0001 for P. histicola (OVA group); p:<0.0001 for CPE group (vehicle vs. P. histicola); ) is a strain of a different genus). In an atopic dermatitis-associated food allergy model using the ovalbumin (OVA) food allergen model, vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") Fig. 3 is a pair of graphs showing anti-OVA IGgl and anti-OVA IgE levels in treated mice (strain A is of a different genus than Prevotella). ovalbumin (OVA) food allergen and vehicle in a contact hypersensitivity model using peanut allergen (CPE) and vehicle, tofacitinib, anti-IL in an atopic dermatitis-associated food allergy model using Prevotella histicola -4, IL-4, IL-5, IL-13, IL-10, and IL-4 in mice treated with Prevotella histicola, or another bacterial species ("strain A") 3 is a series of graphs showing 31 levels (strain A is a strain of a different genus than Prevotella). ovalbumin (OVA) food allergen and vehicle in a contact hypersensitivity model using peanut allergen (CPE) and vehicle, tofacitinib, anti-IL in an atopic dermatitis-associated food allergy model using Prevotella histicola -4, IL-4, IL-5, IL-13, IL-10, and IL-4 in mice treated with Prevotella histicola, or another bacterial species ("strain A") 3 is a series of graphs showing 31 levels (strain A is a strain of a different genus than Prevotella). ovalbumin (OVA) food allergen and vehicle in a contact hypersensitivity model using peanut allergen (CPE) and vehicle, tofacitinib, anti-IL in an atopic dermatitis-associated food allergy model using Prevotella histicola -4, IL-4, IL-5, IL-13, IL-10, and IL-4 in mice treated with Prevotella histicola, or another bacterial species ("strain A") 3 is a series of graphs showing 31 levels (strain A is a strain of a different genus than Prevotella). ovalbumin (OVA) food allergen and vehicle in a contact hypersensitivity model using peanut allergen (CPE) and vehicle, tofacitinib, anti-IL in an atopic dermatitis-associated food allergy model using Prevotella histicola -4, IL-4, IL-5, IL-13, IL-10, and IL-4 in mice treated with Prevotella histicola, or another bacterial species ("strain A") 3 is a series of graphs showing 31 levels (strain A is a strain of a different genus than Prevotella). ovalbumin (OVA) food allergen and vehicle in a contact hypersensitivity model using peanut allergen (CPE) and vehicle, tofacitinib, anti-IL in an atopic dermatitis-associated food allergy model using Prevotella histicola -4, IL-4, IL-5, IL-13, IL-10, and IL-4 in mice treated with Prevotella histicola, or another bacterial species ("strain A") 3 is a series of graphs showing 31 levels (strain A is a strain of a different genus than Prevotella). Atopic dermatitis-associated food allergy model using peanut allergen (CPE) as food allergen, ovalbumin (OVA) food allergen, and vehicle, and Prevotella histicola Ear IL-4 RNA levels, IL-5 RNA levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in models; 4 is a series of graphs showing TSLP RNA levels, CCR4 RNA levels, and IL-19 RNA levels (strain A is of a different genus than Prevotella). Atopic dermatitis-associated food allergy model using peanut allergen (CPE) as food allergen, ovalbumin (OVA) food allergen, and vehicle, and Prevotella histicola Ear IL-4 RNA levels, IL-5 RNA levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in models; 4 is a series of graphs showing TSLP RNA levels, CCR4 RNA levels, and IL-19 RNA levels (strain A is of a different genus than Prevotella). Atopic dermatitis-associated food allergy model using peanut allergen (CPE) as food allergen, ovalbumin (OVA) food allergen, and vehicle, and Prevotella histicola Ear IL-4 RNA levels, IL-5 RNA levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in models; 4 is a series of graphs showing TSLP RNA levels, CCR4 RNA levels, and IL-19 RNA levels (strain A is of a different genus than Prevotella). MC903 model of induction of type 2 dermatitis and food allergy. The study design of the skin sensitization peanut allergy model is presented. The study design of the skin sensitization peanut allergy model is presented. The study design of the skin sensitization peanut allergy model is presented. FIG. 10 is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling in a skin sensitization peanut allergy model. Figure 3 is a pair of graphs showing total and anti-peanut IgE levels on the day of challenge in mice treated with vehicle, tofacitinib ("Tofa"), or Prevotella histicola in a skin sensitization peanut allergy model. 1 is a pair of graphs showing total and anti-peanut IgG1 levels on the day of challenge in mice treated with vehicle, tofacitinib (“tofa”), or Prevotella histicola in a skin sensitization peanut allergy model. A pair of graphs showing total and anti-peanut IgE levels two weeks after challenge in mice administered vehicle, tofacitinib (“Tofa”), or Prevotella histicola in a skin sensitization peanut allergy model. be. A pair of graphs showing total and anti-peanut IgG1 levels two weeks after challenge in mice administered vehicle, tofacitinib (“Tofa”), or Prevotella histicola in a skin sensitization peanut allergy model. be. A pair of graphs showing total and anti-peanut IgG levels two weeks after challenge in mice administered vehicle, tofacitinib ("Tofa"), or Prevotella histicola in a skin sensitization peanut allergy model. be. Schematic diagram showing the experimental design of the FITC-CHS model. IL-13, IL-4 levels in ex vivo restimulated mesenteric lymph node (mLN) cells from mice treated with vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model; 1 is a series of graphs showing IL-5, IL-31 and IL-33 levels. IL-13, IL-4 levels in ex vivo restimulated mesenteric lymph node (mLN) cells from mice treated with vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model; 1 is a series of graphs showing IL-5, IL-31 and IL-33 levels. IL-1 in ex vivo restimulated ear draining cervical lymph node (cLN) cells from mice treated with vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model 13 is a series of graphs showing IL-13 levels, IL-4 levels, IL-5 levels, IL-31 levels, and IL-33 levels. IL-1 in ex vivo restimulated ear draining cervical lymph node (cLN) cells from mice treated with vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model 13 is a series of graphs showing IL-13 levels, IL-4 levels, IL-5 levels, IL-31 levels, and IL-33 levels. FIG. 3 is a schematic diagram showing the experimental design of an atopic dermatitis model using MC903. Ear measurements over time (left panel) and ear inflammation at day 14 in mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903 ( Right panel) is a pair of graphs. Series showing transcript levels of Tslp, Il5, Il31, Il4, Ccl19, and Ccr4 in ear tissue from mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. is a graph of Series showing transcript levels of Tslp, Il5, Il31, Il4, Ccl19, and Ccr4 in ear tissue from mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. is a graph of FIG. 10 is a graph showing mast cell-related gene (Mcpt1) transcript levels in jejunum from mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. IL-10 levels in mesenteric lymph nodes (left panel) and spleen (right panel) in mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. is a graph showing

As disclosed herein, pharmaceutical compositions comprising bacteria of the genus Prevotella have therapeutic efficacy and are useful in the treatment or prevention of one or more T _H2 -mediated conditions. (ie, for treatment, prophylaxis, or both treatment and prophylaxis). Such T _H2 -mediated conditions include, but are not limited to: allergic rhinitis, asthma, atopic dermatitis, urticaria, angioedema, allergies (e.g., food allergies, insect-induced allergies). , drug allergy), anaphylaxis, and eosinophilia. The pharmaceutical composition may comprise Prevotella histicola bacteria.

DEFINITIONS "Adjuvant" or "adjuvant therapy" refers broadly to agents that affect the immunological or physiological response of a subject (eg, a human). For example, adjuvants may increase the presence of antigen over time or to the region of interest, assisting antigen-presenting cell antigen uptake, activating macrophages and lymphocytes, and supporting cytokine production. be. By altering the immune response, the adjuvant may allow for lower doses of the immunointeractive agent, increasing the efficacy or safety of a particular dose of the immunointeractive agent. For example, adjuvants may prevent T cell depletion and thus enhance the efficacy or safety of certain immunointeractive agents.

"Administration" refers broadly to the route of administration of a composition (eg, 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) administration, intramuscular (IM) administration, and subcutaneous (SC) administration. The pharmaceutical compositions described herein may be, but are not limited to, oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (eg, using any standard patch), intradermal, intraocular, intranasal (intranasal), topical, parenteral, e.g. Including transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., transvaginal and perivaginal), implanted, intravesical, intrapulmonary, intraduodenal, intragastric, and intrabronchial). It can be administered in any form by any effective route, hi preferred embodiments, the pharmaceutical compositions described herein are administered orally, rectally, topically, intravesically, into or near the draining lymph nodes. by injection, intravenously, by inhalation or aerosol, or subcutaneously.In another preferred embodiment, the pharmaceutical compositions described herein are administered orally or administered intravenously.

The term "antibody" as used herein can refer to both intact antibodies and antigen-binding fragments thereof. Intact antibodies are glycoproteins comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (abbreviated herein as _VH ) and a heavy chain constant region. Each light chain comprises a light chain variable region (abbreviated herein as _VL ) and a light chain constant region. The V _H and V _L 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 _VH 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 the binding domains that interact with 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. included.

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 antigen. Examples of binding fragments encompassed by the term "antigen-binding fragment" of an antibody include Fab, Fab', F(ab') ₂ , Fv, scFv, disulfide-bonded Fv, Fd, diabodies, single chain antibodies, NANOBODIES ( ®), isolated CDRH3, and other antibody fragments that retain at least a portion of the variable region of the intact antibody. These antibody fragments can be obtained using conventional recombinant and/or enzymatic techniques and screened for antigen binding in the same manner as intact antibodies.

"Carbohydrate" refers to a sugar or polymer of sugars. The terms "saccharide", "polysaccharide", "carbohydrate" and "oligosaccharide" can be used interchangeably. Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one hydroxyl group on each carbon atom of the molecule. Carbohydrates generally have the molecular formula C _n H _2n O _n . Carbohydrates can be monosaccharides, disaccharides, trisaccharides, oligosaccharides, or polysaccharides. Most basic carbohydrates are simple sugars such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose. Disaccharides are two monosaccharides linked together. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose. Typically, oligosaccharides contain 3-6 monosaccharide units (eg, raffinose, stachyose) and polysaccharides contain 6 or more monosaccharide units. Exemplary polysaccharides include starch, glycogen, and cellulose. Carbohydrates may contain modified saccharide units, such as 2′-deoxyribose with the hydroxyl group removed, 2′-fluororibose with the hydroxyl group replaced by fluorine, or N-acetylglucosamine, nitrogen-containing forms of glucose such as , 2-fluororibose, deoxyribose, and hexose). Carbohydrates can exist in many different forms, such as stereoisomers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.

"Cell proliferation" refers broadly to the influx or expansion of cells in an environment, wherein the cells are substantially absent from the environment prior to administration of the composition (e.g., pharmaceutical composition) and Not present in the composition itself. Cells that augment this environment include immune cells, stromal cells, bacterial cells, and fungal cells.

A "clade" refers to a member of an OUR or phylogenetic tree located downstream of a statistically significant node in the phylogenetic tree. A clade comprises a series of terminal leaves in the phylogenetic tree that are distinct monophyletic evolutionary units and share some degree of sequence similarity.

A "combination" of microorganisms (e.g., bacteria) from two or more microbial strains is defined as the physical coexistence of the microorganisms, either in the same material or in the same product, or in a physically connected product; Including that more than one species is administered or co-localized in time. In some embodiments, one of the plurality of strains is from a Prevotella bacterium, such as Prevotella histicola bacterium.

The term "reduce" or "deplete" means that after treatment a difference of at least 10%, 20%, 30%, 40%, 50%, 60%, as the case may be, when compared to the condition before treatment. %, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000, or change as undetectable . Characteristics that may be decreased include: numbers of immune cells, bacterial cells, stromal cells, myeloid-derived suppressor cells, fibroblasts, metabolites; levels of cytokines; (eg, ear thickness in DTH animal models), or tumor size (eg, tumor size in animal tumor models)).

The term "ecological consortium" exchanges metabolites, in contrast to two species of bacteria that induce host synergy by activating complementary host pathways for improved efficacy. and a group of bacteria that positively co-regulate each other.

As used herein, an "engineered bacterium" is any bacterium that has been genetically altered from its natural state by human activity, and any progeny of such bacteria. Engineered bacteria include, for example, the products of targeted genetic modification, random mutagenesis screening, and directed evolution.

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. A particular epitope can be defined by a particular amino acid sequence to which an antibody can bind.

The term "gene" is used broadly to refer to any nucleic acid associated with a biological function. The term "gene" applies to a particular genomic sequence and the cDNA or mRNA encoded by that genomic sequence.

"Identity" between nucleic acid sequences of two nucleic acid molecules is defined, for example, by 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, SF, Guide to Huge Computers, Mrtin J. Bishop, ed., Academic Press, San Diego, 1994, and Carillo et al.(1988) SIAM J Applied M 37: 48. can be determined as a percentage of identity using known computer algorithms such as the "FASTA" program using default parameters as described in . For example, identity can be determined using the BLAST function of the databases of the National Center for Biotechnology Information. Other commercially or publicly available programs include the DNAStar "MegAlign" program (Madison, Wis.) and the University of Wisconsin Genetics Computer Group (UWG) "Gap" program (Madison Wis.).

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

The term "increase" means that after treatment a difference of at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, as the case may be, when compared to the state before treatment. 80%, 90%, 2x, 4x, 10x, 100x, 10^3x, 10^4x, 10^5x, 10^6x, and/or greater than 10^7x means change. Properties that may be increased include: numbers of immune cells, bacterial cells, stromal cells, myeloid-derived suppressor cells, fibroblasts, metabolites; levels of cytokines; (eg, ear thickness in DTH animal models), or tumor size (eg, tumor size in animal tumor models)).

"Innate immune agonists" or "immune adjuvants" refer to innate immune receptors (e.g., Toll-like receptors (TLRs), NOD receptors, RLPs, C-type lectin receptors, STING-cGAS pathway components, inflammasome complexes ) are small molecules, proteins, or other agents that specifically target For example, LPS is a TLR-4 agonist that is bacterially derived or synthetic, and aluminum can be used as an immunostimulatory adjuvant. Immunological adjuvants are a specific class of a 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-isomer of bis-phosphorothioate analogue 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 TLRRI. Examples of NOD agonists include, but are not limited to: N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide (MDP)), gamma-D-glutamyl-meso-diaminopimelic acid ( iE-DAP), and desmuramyl peptide (DMP).

"Internal transcribed spacers" or "ITS" are non-functional, located between structural ribosomal RNA (rRNA) on common precursor transcripts that are often used in certain fungi to identify eukaryotic species. part of the target RNA. The fungal rRNA, which forms the core of the ribosome, is transcribed as a signal gene and consists of the 8S, 5.8S, and 28S regions, between the 8S and 5.8S regions, and the 5.8S and 28S regions, respectively. ITS 4 and 5 are present. These two intercistronic segments between the 18S and 5.8S regions and the 5.8S and 28S regions are removed by splicing and contain significant interspecies variation 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). Although 18S rDNA has traditionally been used for phylogenetic reconstruction, ITS can serve this function because ITS, although generally highly conserved, are found in most fungal genera and This is because they contain hypervariable regions that possess sufficient nucleotide diversity to distinguish between species.

The term "isolated" or "enriched" means (1) isolated from at least some of the components with which it was originally produced (whether in a natural or experimental setting) and/or (2) include microorganisms or other entities or substances produced, prepared, purified, and/or manufactured by the hand of man. The isolated microorganism has at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80% of the other components with which it was originally associated, About 90% or more can be isolated. In some embodiments, the isolated microorganism is greater than about 80%, greater than about 85%, greater than about 90%, greater than about 91%, greater than about 92%, greater than about 93%, greater than about 94%, about greater than 95%, greater than about 96%, greater than about 97%, greater than about 98%, greater than about 99%, or greater than about 99% pure, eg, substantially free of other components. The terms “purify,” “purifying,” and “purified” are used when first produced or produced (whether e.g., in a natural or experimental setting) or when first Refers to a microorganism or other material that has been isolated from at least some of the components that were associated with it at any time after production. A microorganism or population of microorganisms can be considered purified, such as from a material or environment containing a microorganism or population of microorganisms, when isolated during or after production, wherein the purified microorganism or population of microorganisms is up to about 10%, up to about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more than about 90% of other materials considered to have been released. In some embodiments, the purified microorganism or population of microorganisms is 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 greater than about 99% purity. For the microbial compositions provided herein, one or more of the microbial species present in the composition is one or more other than one or more other species produced and/or present in the material or environment containing the microbial species. can be purified separately from the microorganisms of Microbial compositions and their microbial components are generally purified from residual habitats.

As used herein, "lipid" includes any form of fatty acid such as fats, oils, triglycerides, cholesterol, phospholipids, free fatty acids, and the like. Fats, oils, and fatty acids can be saturated, unsaturated (cis or trans), or partially unsaturated (cis or trans).

The term "LPS mutant or lipopolysaccharide mutant" broadly refers to selecting bacteria that lack LPS. LPS deficiency can result from mutations or disruptions to genes involved in lipid A biosynthesis, such as lpxA, lpxC, and lpxD. Bacteria containing LPS mutations can be resistant to aminoglycosides and polymyxins (polymyxin B and colistin).

"Metabolite," as used herein, refers to any and all molecular compounds, compositions, molecules, ions, cofactors, catalysts, or nutrients that are used as substrates in any cellular or microbial metabolic reaction. , or any compound, composition, molecule, ion, cofactor, catalyst, or nutrient obtained as a product from any cellular or microbial metabolic reaction.

"Microorganism" includes archaea, parasites, bacteria, fungi, microalgae, protozoa, and developmental or life cycle stages associated with these organisms (e.g., vegetative, spore-forming (e.g., sporulating, dormant, and germination), latent, biofilm), natural or engineered organisms. In some embodiments, the microorganism is a bacterium. Examples of gut microbes include: Actinomyces graevenitzii, Actinomyces odontolyticus, Akkermansia muciniphila, Bacteroides caccae ( Ｂａｃｔｅｒｏｉｄｅｓ ｃａｃｃａｅ）、バクテロイデス・フラギリス（Ｂａｃｔｅｒｏｉｄｅｓ ｆｒａｇｉｌｉｓ）、バクテロイデス・プトレディニス（Ｂａｃｔｅｒｏｉｄｅｓ ｐｕｔｒｅｄｉｎｉｓ）、バクテロイデス・シータイオタオミクロン（Ｂａｃｔｅｒｏｉｄｅｓ ｔｈｅｔａｉｏｔａｏｍｉｃｒｏｎ）、バクテロイデス・ブルターガス（Ｂａｃｔｅｒｏｉｄｅｓ ｖｕｌｔａｇｕｓ）、ビフィドバクテリウム・アドレスセンティス（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ ａｄｏｌｅｓｃｅｎｔｉｓ）、ビフィドバクテリウム・ビフィドゥム（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ ｂｉｆｉｄｕｍ）、ビロフィラ・ワーズワーシア（Ｂｉｌｏｐｈｉｌａ ｗａｄｓｗｏｒｔｈｉａ）、ブラウティア（Ｂｌａｕｔｉａ）、ブチリビブリオ（Ｂｕｔｙｒｉｖｉｂｒｉｏ）、カンピロバクター・グラシリス（Ｃａｍｐｙｌｏｂａｃｔｅｒ ｇｒａｃｉｌｉｓ）、クロストリジア・クラスターＩＩＩ（Ｃｌｏｓｔｒｉｄｉａ ｃｌｕｓｔｅｒ ＩＩＩ）、クロストリジア・クラスターClostridia cluster IV, Clostridia cluster IX (Acidaminococcaceae group), Clostridia cluster XI, Clostridia cluster XIII (Clustridia cluster XIII) Peptostreptococcus group, Clostridia cluster XIV, Clostridia cluster XV, Collinsella aerofaciens, Copro coccus), Corynebacterium sunsvallense, Desulfomonas pigra, Dorea formicigenerans, Dorea longicatena, Escherichia coli Eubacterium hadrum, Eubacterium rectale, Faecalibacteria prausnitzii, Gemella, Lactococcus, Lachnospira Mulculus (Lanchnospirus cluster), XVI), Mollicutes cluster XVIII, Prevotella, Rothia mucilaginosa, Ruminococcus callidus, Ruminococcus gnavas, Ruminococcus gnavus Ruminococcus torques), and Streptococcus.

"Microbiome" refers broadly to the microorganisms present on or in a body part of a subject or patient. Microorganisms in the microbiome can include bacteria, viruses, eukaryotic microorganisms, and/or viruses. Individual microorganisms in a microbiome can be metabolically active, dormant, dormant, or exist as spores, planktically or in biofilms. available or may exist in the microbiome persistently or transiently. The microbiome may be a commensal or healthy microbiome, or a diseased microbiome. The microbiome may be unique to a subject or patient, or components of the microbiome may be modulated due to changes in health or treatment conditions (e.g., treatment with antibiotics, exposure to various microorganisms). may be introduced, may be depleted. In some aspects, the microbiome occurs on mucosal surfaces. In some aspects, the microbiome is the gut microbiome.

A "microbiome profile" or "microbiome signature" of a tissue or sample refers to at least a partial characteristic of the bacterial structure of the microbiome. In some embodiments, the microbiome profile comprises 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 Indicates the presence or absence of many bacterial strains.

"Modified" with respect to bacteria refers broadly to bacteria that have undergone changes from wild type. Bacterial modification can result from the manipulation of bacteria. Examples of bacterial modifications include genetic modifications, gene expression modifications, phenotypic modifications, formulation modifications, chemical modifications, and doses or concentrations. Examples of improved properties are described throughout the specification and include, for example, attenuation, auxotrophy, homing, or antigenicity. Phenotypic modification can include, for example, bacterial growth in a medium that modifies the bacterial phenotype to increase or decrease virulence.

"Operative taxonomic unit" and "OUU" refer to terminal leaves in the phylogenetic tree that share a nucleic acid sequence (e.g., the entire genome or a specific gene sequence) and sequence identity to this nucleic acid sequence at the species level. Defined by all arrays. In some embodiments, this particular gene sequence may be part of the 16S sequence or the 16 sequence. In other embodiments, the entire genomes of the two entities are sequenced and compared. In another embodiment, selected regions such as multilocus sequence tags (MLSTs), specific genes, or sets of genes can be genetically compared. In the case of 16S, OTUs sharing an average nucleotide identity of 97% or greater over the variable region of the entire 16S or part of the 16S are considered identical OUTs. See, for example: Claesson MJ, Wang Q, O'Sullivan O, 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 JM. 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 sharing an average nucleotide identity of 95% or greater are considered identical OTUs. See for example: 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 JM. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361:1929-1940. OTUs are often 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 nucleotide genes, particularly highly conserved genes (eg, "housekeeping" genes), or combinations thereof. Provided herein are operational taxonomic units (OTUs) that are taxonomically assigned to, for example, genera, species, and phylogenetic clades.

As used herein, a gene that is "overexpressed" in a bacterium means that the bacterium is engineered under at least some conditions more than it is expressed by a wild-type bacterium of the same species under the same conditions. is expressed at higher levels in Similarly, a gene is said to be "underexpressed" in bacteria if it is expressed at a lower level in engineered bacteria under at least some conditions than it is expressed by wild-type bacteria of the same species under the same conditions. is the case.

The terms "polynucleotide" and "nucleic acid" are used interchangeably. They refer to polymeric forms of nucleotides of any length, either deoxyribonucleotides or ribonucleotides or analogs thereof. Polynucleotides can have any three-dimensional structure and can perform any function. The following are non-limiting examples of polynucleotides: coding or non-coding regions of genes or gene fragments, loci defined from linkage analysis, exons, introns, messenger RNAs (mRNAs), microRNAs (miRNAs). , 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 primer. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can 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.

As used herein, "biomarkers" include molecules (eg, mRNA or proteins) whose levels are increased or decreased due to T _H2 -mediated pathways. By way of example, levels of one or more such biomarkers may be elevated in a T _H 2-mediated condition compared to their levels in healthy subjects. Some examples of such protein biomarkers include: interleukin-4, interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-31, interleukin. -33, thymic interstitial 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 interstitial lymphopoietin, and combinations thereof.

As used herein, a substance is "pure" if it is substantially free of other ingredients. The terms “purify,” “purifying,” and “purified” are used to refer to the original or produced (e.g., in nature or in an experimental setting) Refers to a Prevotella bacterial preparation or other material that was originally associated or separated from at least a portion of the associated components over any period of time after initial production. A Prevotella bacterial preparation or composition may be considered purified if, during or after production, it has been isolated from, for example, one or more other bacterial components, the purified microorganism or microorganism The population comprises up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more than about 90% of the other substance. obtained and still considered "refined". In some embodiments, the purified Prevotella bacteria are greater 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 greater than about 99% pure. Prevotella bacterial compositions or preparations are, for example, purified from residual habitat products.

As used herein, the terms "purified Prevotella bacteria" or "Prevotella bacteria composition" are separated from at least one accompanying material found in the raw material. A preparation comprising Prevotella bacteria (e.g., separated from at least one other bacterial strain) or to Prevotella bacteria in any process used to produce the preparation Refers to a preparation containing Prevotella bacteria that has been separated from any accompanying material. The term also refers to compositions that are significantly enriched or concentrated. In some embodiments, the Prevotella bacteria are enriched 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 bacterial composition can be a pharmaceutical composition.

"Residual habitat product" refers to material derived from a microbial habitat in or on a subject. For example, a microbial fermentation culture may contain contaminants, eg, it may contain strains or forms of other microorganisms (eg, bacteria, viruses, mycoplasma, and/or fungi). For example, microorganisms may be found in excretions within the gastrointestinal tract, on the skin itself, in saliva, in the mucus of the respiratory tract, or in secretions of the urogenital tract (i.e., in biological material associated with the microbial community). alive. Substantially free of residual habitat products means that the microbial composition no longer contains biological material associated with the microbial environment on or in the culture or human or animal subject, and any material associated with the microbial community. It means 100% free, 99% free, 98% free, 97% free, 96% free, or 95% free of biological contaminants. Residual habitat products may contain non-living material (eg, undigested food) or may contain unwanted microorganisms. Substantially free of residual habitat products can also mean that the microbial composition is free of culture contaminants or detectable cells from humans or animals, and that only microbial cells are detectable. . In one embodiment, substantially free of residual habitat products also means that the microbial composition is free of detectable viral (e.g., bacterial, viral (e.g., phage)) contaminants, fungal contaminants, mycoplasma contaminants. It can also mean no. In another embodiment, substantially free of residual habitat products is 1 x 10 ^-2 %, 1 x 10 ^-3 %, 1 It means that less than ×10 ⁻⁴ %, 1×10 ⁻⁵ %, 1×10 ⁻⁶ %, 1×10 ⁻⁷ %, 1×10 ⁻⁸ % is human or animal. There are several ways to achieve this purity, without being limited to any of these. Therefore, multiple steps of streaking for single colonies on solid medium are performed until a series of repeat (e.g., but not limited to, two) streaks from single colonies show only single colony morphology. Contamination can be reduced by isolating the desired component via Alternatively, multiple rounds of serial dilution (eg, 10 ⁻⁸ or 10 ⁻⁹ dilutions) on a single desired cell, such as multiple 10-fold serial dilutions, may achieve reduced contamination. This can be further confirmed by showing that multiple isolated colonies have similar cytometric and Gram staining behavior. Other methods of confirming adequate purity include genetic analysis (e.g., PCR, DNA sequencing), serum and antigen analysis, enzymatic and metabolic analysis, and flow cytometry with reagents that distinguish the desired component from contaminants. and the like.

As used herein, "specific binding" refers to the ability of an antibody to bind a predetermined antigen or the ability of a polypeptide to bind to its predetermined binding partner. Typically, an antibody or polypeptide specifically binds its predetermined antigen or binding partner with an affinity corresponding to a K _D of about 10 ⁻⁷ M or less, and non-specific and irrelevant antigen/binding partners. to a given antigen/binding partner with an affinity (expressed as _KD ) that is at least 10-fold less, at least 100-fold less, or at least 1000-fold less than that it binds to (e.g., BSA, casein) Join. Alternatively, specific binding is by a two-component system in which one component is a protein, lipid, or carbohydrate, or combination thereof, and specifically binds to a second component that is a protein, lipid, carbohydrate, or combination thereof. Broadly applicable.

"Strain" refers to a member of a bacterial species that has genetic characteristics that distinguish it from closely related members of the same bacterial species. The genetic characteristic is lack of all or part of at least one gene, lack of all or part of at least one regulatory region (e.g., promoter, terminator, riboswitch, ribosome binding site), absence of at least one natural plasmid. absence (“curing”), presence of at least one recombinant gene, presence of at least one mutated gene, presence of at least one foreign gene (a gene from another species), at least one mutated regulatory region ( For example, the presence of promoters, terminators, riboswitches, ribosome binding sites), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or combinations thereof. Genetic signatures between different strains can be identified by PCR amplification and, optionally, subsequent DNA sequencing of the genomic region of interest or the entire genome. If one strain (compared to another strain of the same species) gains or loses antibiotic resistance, or gains or loses biosynthetic capacity (such as an auxotrophic strain), selection using antibiotics or Strains can be differentiated by counterselection using nutrients/metabolites.

The term "subject" or "patient" refers to any mammal. A subject or patient described as "in need" refers to one in need of treatment (or prevention) of a disease. Mammals (i.e., mammalian animals) include humans, laboratory animals (e.g., primates, rats, mice), farm animals (e.g., cows, sheep, goats, pigs), and domestic pets (e.g., dogs, cats, rodents). type). A subject can be a human. A subject can be a non-human mammal, examples of which include, but are not limited to: dogs, cats, cows, horses, pigs, donkeys, goats, camels, mice, rats, guinea pigs, sheep , llama, monkey, gorilla, or chimpanzee. Subjects may be healthy or afflicted with the condition at any developmental stage, any of which stages may be caused by a condition-associated or causative pathogen or opportunistically favored. are at risk of developing the condition or may transmit condition-associated or condition-causing pathogens to others. In some embodiments, the subject has a T _H2 -mediated condition. In some embodiments, the subject has atopic dermatitis. In some embodiments, the subject has asthma. In some embodiments, the subject has food allergies. In some embodiments, the subject is undergoing treatment for these conditions.

As used herein, the term "treating" a subject disease or "treating" a subject having or suspected of having a condition means that at least one symptom of the condition is alleviated or prevented from exacerbating. As used herein, refers to treating a subject pharmacologically (eg, a pharmaceutical composition), eg, administering one or more agents (eg, pharmaceutical compositions). Thus, in one embodiment, "treating" includes, among other things, slowing progression, promoting remission, inducing remission, enhancing remission, accelerating recovery, increasing efficacy or decreasing resistance to alternative therapeutic agents, or both. refers to a combination of In certain embodiments, the subject experiences a decrease in tumor size, a decrease in tumor number, a decrease in tumor growth, a decrease in cancer metastasis, and/or a decrease in total cancer cell number after treatment beyond what would be expected in the absence of treatment. The cancer is then treated.

Bacteria In certain aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising certain bacteria, and bacterial compositions (e.g., pharmaceutical compositions) using such bacterial compositions (e.g., pharmaceutical compositions) and methods of treating and/or preventing T _H2 -mediated conditions.

In certain embodiments, the pharmaceutical compositions provided herein comprise bacteria of the genus Prevotella. In some embodiments, the bacterium of the genus Prevotella is Prevotella albensis, Prevotella aminii, Prevotella bergensis, Prevotella bivia, Prevotella bivia Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella coprient, Prevotella dentalis, Prevotella dentalis （Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔｉｃｏｌａ）、プレボテラ・ディシエンス（Ｐｒｅｖｏｔｅｌｌａ ｄｉｓｉｅｎｓ）、プレボテラ・ヒスチコーラ（Ｐｒｅｖｏｔｅｌｌａ ｈｉｓｔｉｃｏｌａ）、プレボテラ・メラノゲニカ（Ｐｒｅｖｏｔｅｌｌａ ｍｅｌａｎｏｇｅｎｉｃａ）、プレボテラ・インターメディア（Ｐｒｅｖｏｔｅｌｌａ ｉｎｔｅｒｍｅｄｉａ）、プレボテラ・マクローサ（Ｐｒｅｖｏｔｅｌｌａ ｍａｃｕｌｏｓａ）、プレボテラ・マルシイ（ Ｐｒｅｖｏｔｅｌｌａ ｍａｒｓｈｉｉ）、プレボテラ・メラニノジェニカ（Ｐｒｅｖｏｔｅｌｌａ ｍｅｌａｎｉｎｏｇｅｎｉｃａ）、プレボテラ・マイカンス（Ｐｒｅｖｏｔｅｌｌａ ｍｉｃａｎｓ）、プレボテラ・マルチフォルミス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｆｏｒｍｉｓ）、プレボテラ・ニグレッセンス（Ｐｒｅｖｏｔｅｌｌａ ｎｉｇｒｅｓｃｅｎｓ）、プレボテラ・オラリス（Ｐｒｅｖｏｔｅｌｌａ ｏｒａｌｉｓ）、プレボテラ・オリス（ Prevotella oris, Prevotella aurorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella tanneraeネンシス（Ｐｒｅｖｏｔｅｌｌａ ｔｉｍｏｎｅｎｓｉｓ）、プレボテラ・ジェジュニ（Ｐｒｅｖｏｔｅｌｌａ ｊｅｊｕｎｉ）、プレボテラ・オーランティアカ（Ｐｒｅｖｏｔｅｌｌａ ａｕｒａｎｔｉａｃａ）、プレボテラ・バーロニアエ（Ｐｒｅｖｏｔｅｌｌａ ｂａｒｏｎｉａｅ）、プレボテラ・コロランス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｌｏｒａｎｓ）、プレボテラ・コルポリス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｒｐｏｒｉｓ）、プレボテラ・デンタシニ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｓｉｎｉ）、プレボテラ・エノエカ（Ｐｒｅｖｏｔｅｌｌａ ｅｎｏｅｃａ）、プレボテラ・ファルセニイ（Ｐｒｅｖｏｔｅｌｌａ ｆａｌｓｅｎｉｉ）、プレボテラ・フスカ（Ｐｒｅｖｏｔｅｌｌａ ｆｕｓｃａ）、プレボテラ・ヘパリノリティカ（Ｐｒｅｖｏｔｅｌｌａ ｈｅｐａｒｉｎｏｌｙｔｉｃａ）、プレボテラ・ロエッシェイイ（Ｐｒｅｖｏｔｅｌｌａ ｌｏｅｓｃｈｅｉｉ）、プレボテラ・マルチサッカリボラックス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｓａｃｃｈａｒｉｖｏｒａｘ）、プレボテラ・ナンセイエンシス（Ｐｒｅｖｏｔｅｌｌａ ｎａｎｃｅｉｅｎｓｉｓ）、プレボテラ・オリザエ（Ｐｒｅｖｏｔｅｌｌａ ｏｒｙｚａｅ）、プレボテラ・パルディビエンス（Ｐｒｅｖｏｔｅｌｌａ ｐａｌｕｄｉｖｉｖｅｎｓ）、プレボテラ・プレウリチディス（Ｐｒｅｖｏｔｅｌｌａ ｐｌｅｕｒｉｔｉｄｉｓ）、プレボテラ・ルミニコーラ（Ｐｒｅｖｏｔｅｌｌａ ｒｕｍｉｎｉｃｏｌａ）、プレボテラ・サッカロリティカ（Ｐｒｅｖｏｔｅｌｌａ ｓａｃｃｈａｒｏｌｙｔｉｃａ）、プレボテラ・スコポス（Ｐｒｅｖｏｔｅｌｌａ ｓｃｏｐｏｓ）、プレボテラ・シャーヒイ（Ｐｒｅｖｏｔｅｌｌａ ｓｈａｈｉｉ）、プレボテラ・ズーグレオフォルマンス（Ｐｒｅｖｏｔｅｌｌａ ｚｏｏｇｌｅｏｆｏｒｍａｎｓ）、プレボテラ・ベロラリス（Ｐｒｅｖｏｔｅｌｌａ ｖｅｒｏｒａｌｉｓ）、及び／ or any combination of these species.

In some embodiments, the bacterium of the genus Prevotella is of the species Prevotella histicola.

In some embodiments, the bacterium of the genus Prevotella 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% 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). In some embodiments, the bacterium of the genus Prevotella is Prevotella strain B 50329 (NRRL Accession No. B 50329). As used herein, the term "Prevotella strain B 50329" refers to the strain deposited under NRRL Accession No. B 50329 and strains cloned from and/or derived from the deposited strain. Including both stocks and

Prevotella histicola strain B may be cultured according to methods known in the art. For example, Prevotella histicola, eg, Caballero et al. , 2017. Using the method disclosed in "Cooperating Commons Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium" Cell Host & Microbe 21:592-602, which is incorporated herein by reference in its entirety, ATCC It can be grown on Medium 2722, ATCC Medium 1490, or other media.

In some embodiments, the Prevotella bacterium is one or more species listed in Table 1 (e.g., 1, 2, 3, 4, 5, 6, 7, 8 species, 9 species, 10 species, 11 species, 12 species, 13 species, 14 species, 15 species, 16 species, 17 species, 18 species, 19 species, 20 species, 21 species, 22 species, 23 species, 24 species, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or more) proteins and/or proteins listed in Table 1 encoding 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. In some embodiments, the Prevotella bacterium comprises all of the proteins listed in Table 1 and/or all of the genes encoding the proteins listed in Table 1.

In some embodiments, the Prevotella bacterium is one or more listed in Table 2 (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 and/or one or more of the proteins listed in Table 2 (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) gene-free or substantially free strains of Prevotella bacteria. In some embodiments, the Prevotella bacterium does not comprise all of the proteins listed in Table 2 and/or all of the genes encoding the proteins listed in Table 2.

In some embodiments, the Prevotella bacterium comprises one or more of the proteins listed in Table 1 and does not comprise one or more of the proteins listed in Table 2. or substantially free from strains of Prevotella bacteria. In some embodiments, the Prevotella bacterium comprises all of the proteins listed in Table 1 and/or all of the genes encoding the proteins listed in Table 1 and are listed in Table 2. and/or from strains of Prevotella bacteria that do not contain all of the proteins encoding the proteins listed in Table 2.

Pharmaceutical Compositions In certain embodiments, provided herein, for example, treat or prevent T _H2 -mediated conditions (e.g., atopic dermatitis, asthma, and/or allergy) A pharmaceutical composition comprising a Prevotella bacterium (eg, a Prevotella bacterium described herein) for use in the method. In some embodiments, the Prevotella bacteria composition comprises a combination of Prevotella bacteria and/or bacterial strains described herein and a pharmaceutically acceptable carrier. In some embodiments, the Prevotella bacterial composition comprises a single Prevotella bacterial strain as described herein and a pharmaceutically acceptable carrier.

In some embodiments, the pharmaceutical composition comprises Prevotella bacteria, e.g., Prevotella, plus one or more (e.g., 1, 2, 3, 4, 5 species, 6, 7, 8, 9, 10, or more) bacterial strains or species. In some embodiments, the pharmaceutical composition comprises Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises lyophilized Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises Prevotella bacteria that have been gamma-irradiated. In some embodiments, the pharmaceutical composition comprises live Prevotella bacteria.

In some embodiments, electron microscopy (e.g., EM of ultrathin cryosections) is used to quantify the number of Prevotella bacteria present in a bacterial sample to visualize the bacteria and Relative numbers can be counted. Alternatively, nanoparticle tracking analysis (NTA), Coulter counting, or dynamic light scattering (DLS), or a combination of these techniques may be used. NTA and Coulter counters count particles and indicate their size. DLS gives the size distribution of the particles, but not the concentration. Bacteria often have a diameter of 1-2 um (micrometers). The full range is 0.2-20um. Coulter counting and NTA results can be combined to reveal the number of bacteria in a given sample. Coulter counting reveals the number of particles that are 0.7-10 um in diameter. For most bacterial samples, the Coulter Counter alone can reveal the number of bacteria. For NTA, the Nanosight instrument can be obtained from Malvern Panalytical. For example, the NS300 can visualize and measure particles in suspension in the size range 10-2000 nm. NTA allows counting the number of particles with a diameter of eg 50-1000 nm. DLS reveals a distribution of particles with varying diameters within the approximate range of 1 nm to 3 um.

In some embodiments, Prevotella bacteria can be quantified based on particle count. For example, the total particle count of Prevotella bacteria can be measured using NTA.

In some embodiments, Prevotella bacteria can be quantified based on total cell count (TCC) (eg, determined by Coulter Counter).

In some embodiments, Prevotella bacteria are tested using a plate count assay (e.g., by making serial dilutions of the bacteria, growing them on appropriate media, and then counting the number of colonies). ) can be quantified.

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

In some embodiments, Prevotella bacteria are isolated from, for example, one or more other bacterial components of the source culture. In some embodiments, the pharmaceutical composition further comprises other bacterial components or bacterial strains.

In certain aspects, provided are pharmaceutical compositions for administration to a subject (eg, a human subject). In some embodiments, the pharmaceutical composition is combined with additional actives and/or inactives to produce a final product, which may be a single dosage unit. or may be in a multiple dose format.

In some embodiments the pharmaceutical composition comprises at least one carbohydrate.

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 (18:1) :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).

In some embodiments, the pharmaceutical composition comprises at least one supplemental mineral or mineral source. Examples of minerals include, but are not limited to chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the aforementioned minerals include soluble mineral salts, minor mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals (e.g. carbonyl minerals), and reducing minerals, and combinations thereof.

In some embodiments, the pharmaceutical composition includes at least one supplemental vitamin. The at least one vitamin can be a fat-soluble or water-soluble vitamin. 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 above are salts of vitamins, derivatives of vitamins, compounds with the same or similar activity as vitamins, and metabolites of vitamins.

In some embodiments, the pharmaceutical composition contains excipients. Non-limiting examples of suitable additives include buffers, preservatives, stabilizers, binders, compressing agents, lubricants, dispersion enhancers, disintegrants, flavorants, sweeteners, and colorants.

In some embodiments, this additive is a buffer. Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.

In some embodiments, the additive includes preservatives. Non-limiting examples of suitable preservatives include antioxidants (eg, α-tocopherol and ascorbate), and antimicrobial agents (eg, parabens, chlorobutanol, and phenol).

In some embodiments, the pharmaceutical composition includes a binder as an additive. Non-limiting examples of suitable binders include starch, pregelatinized starch, gelatin, polyvinylpyrrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamide, polyvinyloxoazolidone, polyvinyl alcohol, _C12 - _C18 fatty acids. Alcohols, polyethylene glycols, polyols, sugars, oligosaccharides, and combinations thereof.

In some embodiments, the pharmaceutical composition comprises a lubricant as an additive. Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethylene glycol, sodium benzoate, lauryl sulfate. Sodium, magnesium lauryl sulfate, and light oil.

In some embodiments, the pharmaceutical composition comprises a dispersion enhancing agent as an additive. Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidone, guar gum, kaolin, bentonite, refined wood cellulose, sodium starch glycolate, isoamorphous silicate, and high HLB emulsifier interface. Microcrystalline cellulose is mentioned as an active agent.

In some embodiments, the pharmaceutical composition includes a disintegrant as an additive. 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, microcrystalline cellulose, alginates, Sodium starch glycolate, gums such as agar, gaure, carob, karaya, pectin, and tragacanth. In some embodiments, the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate combined with citric acid and sodium bicarbonate combined with tartaric acid.

In some embodiments, the pharmaceutical composition is a food (e.g., food or drink), for example, health food or drink, food or drink for infants, pregnant women, athletes, the elderly, or certain other Foods or beverages for flocks, functional foods, beverages, foods or beverages for specific health uses, dietary supplements, food or beverages for patients, or animal feed. Specific examples of this food and beverage include: various beverages such as juices, soft drinks, tea beverages, beverage preparations, jelly drinks, and functional drinks; alcoholic beverages such as beer; carbohydrate-containing foods such as , rice foods, noodles, bread, and pasta; paste products such as fish ham, sausage, seafood paste products; products such as milk, dairy drinks, ice cream, cheese and yogurt; fermented products such as fermented miso, yogurt, fermented beverages and pickles; legume products; various confectionery products such as biscuits, cookies and the like , candies, chewing gums, gummies, cold desserts such as jellies, creme caramels, and frozen desserts; instant foods such as instant soups and instant soy soups; microwaveable foods; . Further examples include health foods and health drinks prepared in the form of powders, granules, tablets, capsules, liquids, pastes, and jellies.

In some embodiments, the pharmaceutical composition is food for animals, such as humans. Non-human animals are not particularly limited, and the compositions can be used in a variety of livestock, poultry, pets, laboratory animals, and the like. Examples of such animals include pigs, cows, horses, sheep, goats, chickens, wild ducks, ostriches, ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, and the like, This animal is not limited to these.

Dosage Forms Prevotella bacteria are provided herein for use in methods for treating or preventing, for example, T _H2 -mediated conditions (e.g., atopic dermatitis and/or food allergies). Dosage forms comprising are also provided. Pharmaceutical compositions containing Prevotella bacteria may be formulated, eg, as solid dosage forms for oral administration. The solid dosage form may contain one or more excipients (eg, pharmaceutically acceptable excipients). The Prevotella bacteria in the solid dosage form can be isolated Prevotella bacteria. Optionally, the Prevotella bacteria in the solid dosage form can be lyophilized. Optionally, the Prevotella bacteria in the solid dosage form are live. Optionally, the Prevotella bacteria in the solid dosage form are gamma irradiated. The solid dosage form may comprise tablets, mini-tablets, capsules, pills, or powders; or combinations of these forms (eg, mini-tablets in capsules).

In certain embodiments, the pharmaceutical compositions provided herein are prepared as solid dosage forms comprising Prevotella bacteria and a pharmaceutically acceptable carrier.

In some embodiments, solid dosage forms include capsules. The capsule may contain an enteric coating. The capsules can be size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsules. The capsule may contain Prevotella bacteria powder (eg, Prevotella bacteria that has been lyophilized).

In some embodiments, the solid dosage forms described herein can be, for example, tablets or mini-tablets. In some embodiments, multiple mini-tablets can be present in a capsule (eg, can be filled into a capsule).

In some embodiments, solid dosage forms include tablets (>4 mm) (eg, 5 mm to 17 mm). For example, the tablet is a 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, or 17 mm tablet. This size refers to the diameter of the tablet as known in the art. As used herein, tablet size refers to the size of the tablet prior to application of the enteric coating.

In some embodiments, the solid dosage form comprises mini-tablets. The mini-tablets can range in size from 1 mm to 4 mm, for example, the mini-tablets are 1 mm mini-tablets, 1.5 mm mini-tablets, 2 mm mini-tablets, 3 mm mini-tablets, or 4 mm mini-tablets. could be. This size refers to the diameter of the mini-tablet as is known in the art. As used herein, mini-tablet size refers to the size of the mini-tablet prior to application of the enteric coating.

Mini-tablets can be present in capsules. The capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. Capsules containing mini-tablets may contain a single layer coating, for example a non-enteric coating such as HPMC (hydroxylpropylmethylcellulose) or gelatin. The mini-tablets may reside within a capsule; the number of mini-tablets within the capsule will depend on the size of the capsule and the size of the mini-tablets. As an example, in a size 0 capsule there may be 31-35 mini-tablets (average 33) that are 3 mm mini-tablets.

The solid dosage forms (eg, tablets or mini-tablets) described herein may be enteric coated.

Solid dosage forms may include coatings. Solid dosage forms may include a single layer coating, such as an enteric coating, such as a Eudragit-based coating, such as EUDRAGIT L30 D-55, triethyl citrate, and talc. A solid dosage form may comprise two layers of coating. For example, the inner coating can include, for example, EUDRAGIT L30 D-55, triethyl citrate, talc, citric anhydride, and sodium hydroxide, and the outer coating can include, for example, EUDRAGIT L30 D-55, triethyl citrate, and May contain talc. EUDRAGIT is a brand name for various polymethacrylic acid-based copolymers. EUDRAGIT includes anionic, cationic and neutral copolymers based on methacrylic acid and methacrylic acid/acrylic acid esters or derivatives thereof. Eudragit is an amorphous polymer with a glass transition temperature of 9-150°C. Eudragit is non-biodegradable, non-absorbable and non-toxic. Anionic Eudragit L dissolves at pH>6 and is used for enteric coating, while Eudragit S, which is soluble at pH>7, is used for colon targeting. Eudragit RL and RS with quaternary ammonium groups are water insoluble but swellable/permeable polymers that are suitable for sustained release fill coating applications. Cationic Eudragit E, insoluble at pH≧5, can prevent drug release in saliva.

Solid dosage forms such as capsules may comprise a single layer coating, eg, a non-enteric coating such as HPMC (hydroxylpropylmethylcellulose) or gelatin.

Pharmaceutical compositions containing Prevotella bacteria may be formulated, for example, as suspensions for oral administration or for injection. Administration by injection includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. In the case of suspensions, the Prevotella bacteria can be in a buffer, eg, in a pharmaceutically acceptable buffer such as saline or PBS. The suspension may contain one or more excipients (eg, pharmaceutically acceptable excipients). The suspending agent may contain, for example, sucrose or glucose. The Prevotella bacteria in the suspension can be isolated Prevotella bacteria. Optionally, the Prevotella bacteria in the suspension dosage form can be lyophilized. Optionally, the Prevotella bacteria in the solid dosage form are live. Optionally, the Prevotella bacteria in the suspension can be gamma irradiated.

Dosage For oral administration to a human subject, a dose of Prevotella bacteria can be, for example, from about 2×10 ⁶ to about 2×10 ¹⁶ particles. This dose is, for example, about 1×10 ⁷ to about 1×10 ¹⁵ , about 1×10 ⁸ to about 1×10 ¹⁴ , about 1×10 ⁹ to about 1×10 ¹³ , about 1×10 ¹⁰ from about 1×10 ¹⁴ , or from about 1×10 ⁸ to about 1×10 ¹² particles. This dose is, for example, about 2 x ¹⁰⁶ , about 2 x ¹⁰⁷ , about 2 x ¹⁰⁸ , about 2 x 109, about ¹ x ¹⁰¹⁰ , about 2 x ¹⁰¹⁰ , about 2 It can be about 2 x 10 ¹² , about 2 x ^{10 13 ,} about 2 x 10 ¹⁴ , or about 1 x 10 ¹⁵ particles. This dose can be, for example, about 2×10 ¹⁴ particles. This dose can be, for example, about 2×10 ¹² particles. The particles can be, for example, about 2×10 ¹⁰ particles. The particles can be, for example, about 1×10 ¹⁰ particles. Particle numbers can be determined, for example, by NTA.

For oral administration to human subjects, dosages of Prevotella bacteria can be based, for example, on total protein. This dose can be, for example, from about 5 mg to about 900 mg of total protein. This dose can be, for example, from about 20 mg to about 800 mg, from about 50 mg to about 700 mg, from about 75 mg to about 600 mg, from about 100 mg to about 500 mg, from about 250 mg to about 750 mg, or from about 200 mg to about 500 mg of total protein. This dose is, for example, 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. obtain. This dose can be, for example, about 10 mg of total protein. Total protein can be determined by, for example, the Bradford assay or the BCA assay.

For administration by injection (eg, intravenous administration) to a human subject, a dose of Prevotella bacteria can be, for example, from about 1×10 ⁶ to about 1×10 ¹⁶ particles. This dose is, for example, about 1×10 ⁷ to about 1×10 ¹⁵ , about 1×10 ⁸ to about 1×10 ¹⁴ , about 1×10 ⁹ to about 1×10 ¹³ , about 1×10 ¹⁰ from about 1×10 ¹⁴ , or from about 1×10 ⁸ to about 1×10 ¹² particles. This dose is, for example, about 2 x ¹⁰⁶ , about 2 x ¹⁰⁷ , about 2 x ¹⁰⁸ , about 2 x 109, about ¹ x ¹⁰¹⁰ , about 2 x ¹⁰¹⁰ , about 2 It can be about 2 x 10 ¹² , about 2 x ^{10 13 ,} about 2 x 10 ¹⁴ , or about 1 x 10 ¹⁵ particles. This dose can be, for example, about 1×10 ¹⁵ particles. This dose can be, for example, about 2×10 ¹⁴ particles. This dose can be, for example, 2×10 ¹³ particles. Particle numbers can be determined, for example, by NTA.

For administration by injection (eg, intravenous administration), a dose of Prevotella bacteria can be, for example, from about 5 mg to about 900 mg of total protein. This dose can be, for example, from about 20 mg to about 800 mg, from about 50 mg to about 700 mg, from about 75 mg to about 600 mg, from about 100 mg to about 500 mg, from about 250 mg to about 750 mg, or from about 200 mg to about 500 mg of total protein. This dose can be, for example, 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. . This dose can be, for example, about 700 mg of total protein. This dose can be, for example, about 350 mg of total protein. This dose can be, for example, about 175 mg of total protein. Total protein can be determined by, for example, the Bradford assay or the BCA assay.

In certain embodiments, the pharmaceutical composition (e.g., a total dose of the composition administered, e.g., once or twice daily) contains at least 1 x 10 ¹⁰ total cells (e.g., at least 1 x 10 ¹⁰ total cells, at least 2 x 10 ¹⁰ total cells, at least 3 x 10 ¹⁰ total cells, at least 4 x 10 ¹⁰ total cells, at least 5 x 10 ¹⁰ total cells, at least 6 x 10 Prevotella of ¹⁰ total cells, at least 7×10 ¹⁰ total cells, at least 8×10 ¹⁰ total cells, at least 9×10 ¹⁰ total cells, at least 1×10 ¹¹ total cells In some embodiments, the pharmaceutical composition comprises 9 x 10 ¹¹ total cells or less (e.g., 1 x 10 ¹⁰ total cells or less, 2 x 10 ¹⁰ total cells or less, 3 x 10 10 total cells or less, 3 ×10 ¹⁰ or less total cells, 4 × 10 ¹⁰ or less total cells, 5 × 10 ¹⁰ or less total cells, 6 × 10 ¹⁰ or less total cells, 7 × 10 ¹⁰ or less total cells, 8 ×10 ¹⁰ or less total cells, 9 × 10 ¹⁰ or less total cells, 1 × 10 ¹¹ or less total cells, 2 × 10 ¹¹ or less total cells, 3 × 10 ¹¹ or less total cells, 4 ×10 ¹¹ or less total cells, 5 × 10 ¹¹ or less total cells, 6 × 10 ¹¹ or less total cells, 7 × 10 ¹¹ or less total cells, 8 × 10 ¹¹ or less total cells) Prevotella bacteria, hi some embodiments, the pharmaceutical composition comprises about 6×10 ⁹ total cells of Prevotella bacteria, hi some embodiments, the pharmaceutical composition comprises contains about 1.6 x 10 ¹⁰ total cells of Prevotella bacteria, hi some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹⁰ total cells of Prevotella bacteria In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹¹ total cells of Prevotella bacteria, hi some embodiments, the pharmaceutical composition comprises about 3.2 x 10 ¹¹ total cells of Prevotella bacteria, hi some embodiments, the pharmaceutical composition comprises about 8 x 10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition contains about 1.6×10 ¹⁰ to about 8×10 ¹¹ total cells of Prevotel la) contains bacteria; In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹⁰ to about 1.6×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 8×10 ¹⁰ to about 8×10 ¹¹ total cells of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises about 1.6×10 ¹¹ to about 8×10 ¹¹ total cells of Prevotella bacteria.

In certain embodiments, provided herein are solid dosage forms comprising Prevotella bacteria. In some embodiments, the solid dosage form includes an enteric coating. In some embodiments, the solid dosage form is a capsule, eg, an enteric coated capsule. In some embodiments, each capsule contains about 8×10 ¹⁰ total cells of Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered to a subject, eg, once or twice daily. In some embodiments, one capsule (eg, containing about 8×10 ¹⁰ total cells) is administered to the subject, eg, once or twice daily. In some embodiments, two capsules (eg, each containing about 8×10 ¹⁰ total cells) are administered to the subject, eg, once or twice daily. In some embodiments, 4 capsules (eg, each containing about 8×10 ¹⁰ total cells) are administered to a subject, eg, once or twice daily. In some embodiments, 10 capsules (eg, each containing about 8×10 ¹⁰ total cells) are administered to a subject, eg, once or twice daily. In some embodiments, the Prevotella bacteria in the capsule are lyophilized (eg, in powder form).

In some embodiments, solid dosage forms include capsules. In some embodiments, the capsule is an enteric coated tablet. In some embodiments, the capsule comprises about 8×10 ¹⁰ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the capsule comprises about 1.6×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the capsule comprises about 3.2×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the capsule comprises about 8×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one capsule or multiple capsules). In some embodiments, the Prevotella bacteria in the capsule are lyophilized (eg, in powder form).

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 tablets are 5 mm to 17 mm in diameter. In some embodiments, the tablet comprises about 8×10 ¹⁰ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the tablet comprises about 1.6×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the tablet comprises about 3.2×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the tablet comprises about 8×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of one tablet or multiple tablets). In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

In some embodiments, the solid dosage form comprises mini-tablets. In some embodiments, the mini-tablets are enteric coated. In some embodiments, the mini-tablets are 1 mm to 4 mm in diameter. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) are 1 mm mini-tablets, 1.5 mm mini-tablets, 2 mm mini-tablets, 3 mm mini-tablets, or 4 mm mini-tablets. is. In some embodiments, the solid dosage form comprises mini-tablets comprising about 8×10 ¹⁰ total cells of Prevotella bacteria (eg, a total dose of a plurality of mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets comprising about 1.6×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of multiple mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets comprising about 3.2×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of multiple mini-tablets). In some embodiments, the solid dosage form comprises mini-tablets comprising about 8×10 ¹¹ total cells of Prevotella bacteria (eg, a total dose of a plurality of mini-tablets). In some embodiments, the Prevotella bacteria in the mini-tablets are lyophilized. In some embodiments, mini-tablets (eg, enteric-coated mini-tablets) are in capsules. 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 (eg, is coated with) a non-enteric coating (eg, HPMC (hydroxylpropylmethylcellulose) or gelatin). In some embodiments, the capsule includes a non-enteric coating. In some embodiments, the capsule comprises hydroxylpropylmethylcellulose (HPMC). In some embodiments, the capsule contains gelatin. In some embodiments, a mini-tablet (e.g., an enteric-coated mini-tablet) comprising about 8 x 10 ¹¹ total cells of Prevotella bacteria is encased in a capsule, optionally comprising: The capsule contains HPMC.

Gamma Irradiation Powders (eg, Prevotella bacterial powders) can be gamma irradiated at 17.5 kGy radiation units at ambient temperature.

Frozen biomass (eg, biomass of Prevotella bacteria) can be gamma-irradiated at 25 kGy radiation units in the presence of dry ice.

T _H2 -mediated conditions As T _H2 (type 2)-mediated conditions that can be treated and/or prevented by Prevotella bacteria (e.g., pharmaceutical compositions thereof), e.g. levels of interleukin (IL)-4, IL-5, IL-13, IL-19, IL-21, IL-31, IL-33, and/or TSLP (thymic stromal lymphopoietin) in For example, conditions associated with elevated mRNA levels or protein levels).

Prevotella bacteria (eg, pharmaceutical compositions thereof) are 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 levels or protein levels) can be reduced, e.g. cause a decrease compared to levels in the absence of (or prior to) administration of the pharmaceutical composition thereof). The pharmaceutical composition can reduce these levels by, for example, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%.

IgG1, as T _H2 (type 2)-mediated conditions that can be treated and/or prevented by Prevotella bacteria (e.g., pharmaceutical compositions thereof), e.g., during the development or course of the disease; Conditions with elevated levels of IgE and/or IgA (eg, mRNA levels or protein levels) are included.

A Prevotella bacterium (e.g., a pharmaceutical composition thereof) can reduce levels of IgG1, IgE, and/or IgA (e.g., mRNA levels or protein levels), e.g., a Prevotella bacterium (e.g., a pharmaceutical composition thereof). pharmaceutical composition) causes a decrease compared to the level in the absence of (or prior to) administration of the Prevotella bacterium (eg, the pharmaceutical composition thereof). The pharmaceutical composition can reduce these levels by, for example, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%.

T _H2 -mediated conditions can include asthma, atopic dermatitis, eosinophilic disease, or allergies (eg, seasonal allergies, pet allergies, or food allergies). The allergies may include food allergies, seasonal allergic rhinitis, or pet allergies. The food allergy may include peanut allergy. The food allergy may include milk allergy, egg allergy, fish allergy, crustacean shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. The food allergy may include allergy to food antigens. The food antigens may include peanut antigens. The food allergy may include allergy to food antigens, and the food antigens may include milk antigens, egg antigens, fish antigens, shellfish antigens, tree nut antigens, wheat antigens, or soybean antigens.

Some of the specific T _H 2-mediated conditions are described in further detail below.

Allergic Rhinitis In some embodiments, the T _H2 -mediated condition includes allergic rhinitis (ie, hay fever). Allergic rhinitis occurs when allergens cause inflammation in the nose. Types of potential allergens, individually or in combination, include pollen, pet hair, dander, dust mites, mold, smoke, and perfume. Symptoms of allergic rhinitis may include, individually or in combination, a runny or stuffy nose; itchy eyes, mouth, throat, or skin; sneezing: coughing; and malaise.

Asthma In some embodiments, the T _H2 -mediated condition includes asthma (eg, allergic asthma). Asthma occurs, for example, when the airways in the lungs become inflamed. One type of asthma included in the conditions relevant to this disclosure is atopic asthma. Symptoms of asthma, individually or in combination, may include coughing, wheezing, shortness of breath, and chest tightness.

Atopic Dermatitis In some embodiments, the T _H 2-mediated condition includes atopic dermatitis (ie, eczema). Atopic dermatitis occurs when the skin becomes inflamed. Atopic dermatitis can be complicated by allergic rhinitis and/or asthma. Symptoms of atopic dermatitis may include, individually or in combination, dry skin, redness, itching, rashes, and sores.

Urticaria In some embodiments, the T _H2 -mediated condition includes urticaria (ie, hives). Hives occur when the skin develops swollen, red welts. This condition can be caused by leakage of plasma from blood vessels due to histamine, for example as a result of an allergic reaction. Symptoms of urticaria may include, individually or in combination, lumps of welts, itching, and swelling.

Angioedema In some embodiments, the T _H 2-mediated condition includes angioedema (ie, deep tissue swelling). If this swelling is under the skin, a condition that is otherwise similar to urticaria can be classified as angioedema. This condition can be caused by leakage of plasma from blood vessels due to histamine, for example as a result of an allergic reaction. Symptoms of angioedema may include, individually or in combination, swelling of the eyes, mouth, hands, feet, or throat; difficulty breathing; and stomach cramps.

Food Allergy In some embodiments, the T _H2 -mediated condition includes food allergy. Food allergies occur when a food (eg, its allergen) provokes an abnormal immune response. Typical types of foods that can cause reactions include eggs, milk, peanuts, tree nuts (eg walnuts), fish, shellfish, wheat, and soybeans. In addition, seeds (eg sesame, mustard), fruits and rice can also cause food allergies. Symptoms may include, individually or in combination, itching in the mouth; hives; swelling in areas of the body such as the face; difficulty breathing; abdominal discomfort; and dizziness.

Insect-Induced Allergy In some embodiments, the T _H2 -mediated condition includes insect-induced allergy. Insect-induced allergies occur when the immune system reacts to an insect bite or bite. Typical types of insects that can provoke such reactions include wasps, honey bees, hornets, yellow-jacket, ants, mosquitoes, bed bugs, fleas, and ticks.

Drug Allergy In some embodiments, the T _H2 -mediated condition includes drug allergy. Drug allergy occurs as an adverse reaction upon exposure to drugs. Some classes of drugs that can cause such reactions include penicillins, sulfonamides, anticonvulsants, aspirin, and chemotherapeutic agents. Symptoms of drug allergy, individually or in combination, may include fever, itching, hives, rash, swelling, and shortness of breath.

Anaphylaxis In some embodiments, the T _H 2-mediated condition includes anaphylaxis. Anaphylaxis occurs when reactions to food, insect venoms, or drugs are severe. Anaphylaxis can affect the whole body and can alter breathing, blood pressure, and heart rate.

Eosinophilia In some embodiments, T _H2 -mediated conditions include eosinophilia (eg, primary eosinophilia). Eosinophilia occurs when the number of eosinophils at a particular site or in peripheral blood exceeds a certain threshold.

For each of these T _H 2-mediated conditions, the symptoms of the particular T _H 2-mediated condition treated by the methods described herein for treating or preventing such conditions. may result in a reduction, stabilization, or other amelioration of the symptoms, including those described herein.

Additional Therapeutic Agents In certain aspects, the methods provided herein can be used to treat a T _H2 -mediated condition (e.g., atopic dermatitis and/or food allergy) alone or with another therapeutic agent. subject to bacteria and/or bacterial compositions (e.g., pharmaceutical compositions containing Prevotella bacteria) described herein in combination with another therapeutic agent for treating or preventing including administration to A pharmaceutical composition comprising Prevotella bacteria can be administered, for example, in combination with an anti-inflammatory agent. The anti-inflammatory agents include antihistamines (e.g., cetirizine, fexofenadine, or diphenhydramine), epinephrine, corticosteroids (oral or topical) (e.g., betamethasone valerate, hydrocortisone, or prednisone), calcineurin inhibitors (e.g., tacrolimus or pimecrolimus), cyclosporine, interferon gamma-1b, or dupilumab. Topical corticosteroids that may be used include: alclomethasone propionate, betamethasone propionate, betamethasone valerate, clobetasol propionate, desonide, desoxymethasone fluocinolone acetonide, Fluocinonide, fluticasone propionate, halobetasol propionate, hydrocortisone, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, triamcinolone acetonide, and triamcinolone acetate.

In some embodiments, the Prevotella bacterium-containing pharmaceutical composition and the other treatment may be administered to the subject in any order. In some embodiments, the pharmaceutical composition containing Prevotella bacteria and the other treatment are administered together.

In some embodiments, the pharmaceutical composition containing Prevotella bacteria is administered prior to administration of the additional therapeutic agent (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 ago, 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 prior to . In some embodiments, the pharmaceutical composition containing Prevotella bacteria is administered after administration of an additional therapeutic agent (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, after 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, 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 later). . In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the additional therapeutic agent are administered to the subject at or near the same time (eg, administration within one hour of each other). In some embodiments, prior to administering a pharmaceutical composition containing Prevotella bacteria to a 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 prior to administration of antibiotics to the subject. do. In some embodiments, after administering a pharmaceutical composition containing Prevotella bacteria to a 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 administration of antibiotics to the subject. do. In some embodiments, the Prevotella bacterium-containing pharmaceutical composition and the antibiotic are administered to the subject at or near the same time (eg, administration within 1 hour of each other).

In certain embodiments, the subject may have undergone surgery. Types of surgery include, but are not limited to, prophylactic surgery, diagnostic or staging surgery, curative surgery, and symptomatic surgery.

In some embodiments, the additional therapeutic agent is an antibiotic. "Antibiotics" refers broadly to compounds capable of inhibiting or preventing bacterial infections. Classify antibiotics in different ways (e.g., use for specific infections, mechanism of action, bioavailability, spectrum of target organisms (e.g., Gram-negative versus Gram-positive, aerobe versus anaerobe)) This antibiotic can be used to kill specific bacteria in specific regions (“niches”) of the host (Leekha, et al 2011. General Principles of Antimicrobial Therapy. Mayo Clin Proc. 86 (2 ): 156-167). In certain embodiments, antibiotics may be used to selectively target specific niche bacteria. In some embodiments, antibiotics are administered after bacterial treatment. In some embodiments, antibiotics are administered after bacterial treatment to eliminate engraftment.

In some aspects, antibiotics may be selected based on their bactericidal or bacteriostatic properties. Bactericidal antibiotics include those that disrupt cell walls (eg, β-lactams), disrupt cell membranes (eg, daptomycin), or disrupt bacterial DNA (eg, fluoroquinolones). Bacteriostatic agents inhibit bacterial replication and include sulfonamides, tetracyclines, and macrolides, and act by inhibiting protein synthesis. Furthermore, while some agents may be bactericidal in certain organisms and bacteriostatic in others, knowledge of the target organism allows the skilled artisan to select antibiotics with appropriate properties. can. In certain treatment conditions, bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics. Therefore, in certain embodiments, bactericidal and bacteriostatic antibiotics are not combined.

Antibiotics include, but are not limited to: aminoglycosides, ansamycins, carbacephems, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactam, nitrofurans, oxazolidonones, penicillins, polypeptides Antibiotics, quinolones, fluoroquinolones, sulfonamides, tetracyclines, and antimycobacterial compounds, and combinations thereof.

Aminoglycosides include, but are not limited to: amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, and spectinomycin. Aminoglycosides are, for example, against Gram-negative bacteria such as Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis, as well as certain aerobic bacteria. Effective, but less effective against obligate/facultative anaerobes. Aminoglycosides are believed to bind to bacterial 30S or 50S ribosomal subunits, thereby inhibiting bacterial protein synthesis.

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.

Carbacephems include, but are not limited to, loracarbef. Carbacephem is believed to inhibit bacterial cell wall synthesis.

Carbapenems include, but are not limited to, ertapenem, doripenem, imipenem/cilastatin, and meropenem. As broad-spectrum antibiotics, carbapenems are bactericidal against both Gram-positive and Gram-negative bacteria. Carbapenems are believed to inhibit bacterial cell wall synthesis.

Cephalosporins include, but are not limited to: Cefadroxil, Cefazolin, Cefalothin, Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone , cefotaxime, cefpodoxime, ceftazidime, ceftibutene, ceftizoxime, ceftriaxone, cefepime, ceftaroline fosamil, and ceftobiprol. Certain cephalosporins are effective against, for example, Gram-negative and Gram-positive bacteria (e.g., Pseudomonas), and certain cephalosporins are effective against methicillin-resistant Staphylococcus aureus (MRSA). ). Cephalosporins are believed to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

Glycopeptides include, but are not limited to, teicoplanin, vancomycin, and telavancin. Glycopeptides are effective, for example, against aerobic and anaerobic Gram-positive bacteria (eg, MRSA and Clostridium difficile). Glycopeptides are believed to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

Lincosamides include, but are not limited to, clindamycin and lincomycin. Lincosamides are effective, for example, against anaerobic bacteria and Staphylococcus and Streptococcus. Lincosamides are believed to bind to the bacterial 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Lipopeptides include, but are not limited to, daptomycin. Lipopeptides are effective, for example, against Gram-positive bacteria. Lipopeptides are thought to bind to bacterial membranes and cause rapid depolarization.

Macrolides include, but are not limited to: azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, and spiramycin. Macrolides are effective, for example, against Streptococcus and Mycoplasma. Macrolides are believed to bind to bacterial subunits or 50S ribosomal subunits, thereby inhibiting bacterial protein synthesis.

Monobactams include, but are not limited to, aztreonam. Monobactam is effective, for example, against Gram-negative bacteria. Monobactam is believed to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

Nitrofurans include, but are not limited to, furazolidone and nitrofurantoin.

Oxazolidnones include, but are not limited to: Linezolid, Posizolid, Radezolid, and Torezolid. Oxazolidnones are believed to be protein synthesis inhibitors.

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 against, for example, Gram-positive bacteria, facultative anaerobes, and are effective against, for example, Streptococcus, Borrelia, and Treponema. Penicillin is believed to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

Penicillin combinations include, but are not limited to: amoxicillin/clavulanic acid, ampicillin/sulbactam, piperacillin/tazobactam, and ticarcillin/clavulanic acid.

Polypeptide antibiotics include, but are not limited to: bacitracin, colistin, and polymyxins B and E. Polypeptide antibiotics are effective, for example, against Gram-negative bacteria. Certain polypeptide antibiotics inhibit isoprenyl pyrophosphate, which is involved in the synthesis of the peptidoglycan layer of the bacterial cell wall, while others are thought to destabilize the bacterial outer membrane by displacing the bacterial counterion. ing.

Quinolones and fluoroquinolones include, but are not limited to: ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin, Glepafloxacin, Sparfloxacin, and Temafloxacin. Quinolones/fluoroquinolones are effective against, for example, Streptococcus and Neisseria. The quinolones/fluoroquinolones are believed to inhibit bacterial DNA gyrase or topoisomerase IV, thereby inhibiting DNA replication and transcription.

Sulfonamides include, but are not limited to: Mafenide, Sulfacetamide, Sulfadiazine, Silver Sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim. - sulfamethoxazole (cotrimoxazole), and sulfonamide chrysoidine. Sulfonamides are believed to inhibit folate synthesis through competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.

Tetracyclines include, but are not limited to: demeclocycline, doxycycline, minocycline, oxytetracycline, and tetracycline. Tetracycline is effective against Gram-negative bacteria, for example. Tetracycline is believed to bind to the bacterial 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Anti-mycobacterial compounds include, but are not limited to: clofazimine, dapsone, capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide, rifampicin, rifabutin, rifapentin, and streptomycin.

Suitable antibiotics also include: arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin/clavulanic acid, ampicillin. /sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin P1, clarithromycin, erythromycin, furazolidone, fusidic acid, sodium fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazole , micamycin, mutacin B-Ny266, mutacin B-JHl 140, mutacin J-T8, nisin, nisin A, novobiocin, oleandomycin, ostreoglycin, piperacillin/tazobactam, pristinamycin, ramoplanin, lanalexin, reuterin, rifaximin, rosamicin, rosalamycin, spectinomycin, spiramycin, stafilomycin, streptogramin, streptogramin A, synergistin, taurolidine, teicoplanin, telithromycin, ticarcillin/clavulanic acid, triacetyloleandomycin, tylosin, tyrosidine, tyrosthricin, vancomycin, vemamycin, and virginiamycin.

In some embodiments, the additional therapeutic agent is administered to the subject with therapeutic bacteria (eg, Prevotella bacteria) and/or therapeutic combinations of bacteria such that a healthy microbiome can be reconstituted in the subject. including administering. In some embodiments, the therapeutic bacteria are probiotic bacteria.

Some of the specific additional therapeutic agents are detailed further below.

Allergic Rhinitis In some embodiments, the T _H2 -mediated condition includes allergic rhinitis and the additional therapeutic agent includes agents 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, chlorcyclidine, chloropyramine, chlorphenamine, clemastine, cyclidine, cyproheptadine, desloratadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimethindene, diphenhydramine, doxylamine, ebastine, fexofenadine, hydroxyzine, ketotifen, levocabastine, levocetirizine, loratadine, meclizine, mepyramine, mizolastine, olopatadine, orphenadrine, pheniramine, promethazine, kifenadine, rupatadine, terfenadine, tripelennamine, triprolidine), mast cell stabilizer (e.g. cromolyn), decongestants (e.g. beclomethasone, budesonide, ciclesonide, dexamethasone, ephedrine, flunisolide, fluticasone, fluticasone furoate, fluticasone propionate, levomethasone, mometasone, naphazoline, oxymetazoline, phenylephrine, phenylpropanol amines, prednisolone, propylhexedrine, pseudoephedrine, synephrine, tetrizoline, thixocortol, tramazolin, triamcinolone, triamcinolone acetonide, xylometazoline), leukotriene receptor antagonists (e.g. montelukast, zafirlukast, zileuton, MK-886, meclofenamic acid) sodium), and immunotherapeutic agents (eg, immunotherapeutic agents including forms of the allergen itself, immunotherapeutic agents including forms of antibodies such as omalizumab). These agents may also be used in general for other types of allergy, which may occur as a single type of allergy or in combination with other types of allergy.

Asthma In some embodiments, the T _H2 -mediated condition includes asthma (eg, allergic asthma) and the additional therapeutic agent includes agents that can be used to treat asthma. Such agents include, individually or in combination: corticosteroids, decongestants (some are also corticosteroids), mast cell stabilizers, leukotriene modulators, and treatment of allergic rhinitis. An immunotherapeutic agent provided herein for In addition, for asthma, the agents also include, individually or in combination: beta agonists (e.g. salmeterol, formoterol, albuterol, levalbuterol), certain corticosterone and beta agonist combinations (e.g. fluticasone-salmeterol, budesonide-formoterol, budesonide-formoterol, formoterol-mometasone), additional immunotherapeutic agents (eg, mepolizumab, dupilumab, reslizumab, and benralizumab), and certain other drugs (eg, theoferline, ipratropium). These agents may be provided by use of an inhaler, as injections (eg, injections for antibody forms), or as pills (eg, sublingual tablets for allergen immunotherapy).

Atopic Dermatitis In some embodiments, the T _H2 -mediated condition includes atopic dermatitis and the additional therapeutic agent includes agents that can be used to treat atopic dermatitis. Such agents include, individually or in combination, corticosteroids (eg, prednisone) and immunotherapeutic agents (eg, dupilumab) provided herein for the treatment of allergic rhinitis or asthma. In addition, for atopic dermatitis, this agent also includes: calcineurin inhibitors (e.g. tacrolimus, pimecrolimus), certain nutritional supplements (e.g. vitamin D), immunosuppressants (e.g. cyclosporine, methotrexate). , interferon gamma-1b, mycophenolate mofetil, azathioprine), and other drugs (eg, crisabolol).

Urticaria In some embodiments, the T _H2 -mediated condition includes urticaria and the additional therapeutic agent includes an agent that can be used to treat urticaria. Such agents include, individually or in combination, antihistamines provided herein for the treatment of allergic rhinitis or asthma (e.g., diphenhydramine, loratadine, fexofenadine, cetirizine, desloratadine), corticosteroids ( prednisone), leukotriene receptor antagonists, and immunotherapeutic agents (eg omalizumab). In addition, for urticaria, the drug may also include: other antihistamines (e.g. ranitidine, cimetidine, famotidine), immunosuppressants (e.g. cyclosporine, tacrolimus, sirolimus, mycophenolic acid), anti-inflammatory Drugs (eg, dapsone, sulfasalazine, hydroxychloroquine), corticosteroids (eg, cortisone), and hormones (eg, epinephrine).

Angioedema In some embodiments, the T _H2 -mediated condition includes angioedema and the additional therapeutic agent includes agents that can be used to treat angioedema. Such agents include, individually or in combination, antihistamines provided herein for the treatment of allergic rhinitis or asthma (e.g., diphenhydramine, loratadine, fexofenadine, cetirizine, desloratadine), corticosteroids ( prednisone), leukotriene receptor antagonists, and immunotherapeutic agents (eg omalizumab). In addition, for angioedema, the agent may also include: other antihistamines (e.g. ranitidine, cimetidine, famotidine), immunosuppressants (e.g. cyclosporine, tacrolimus, sirolimus, mycophenolic acid), anti-inflammatory agents. (eg dapsone, sulfasalazine, hydroxychloroquine), corticosteroids (eg cortisone), and hormones (eg epinephrine).

Food Allergy In some embodiments, the T _H 2-mediated condition includes food allergy and the additional therapeutic agent includes agents that can be used to treat food allergy. Such agents include, individually or in combination, epinephrine, antihistamines, glucocorticoid steroids, immunotherapeutic agents (e.g., immunotherapeutic agents including forms of the allergen itself, immunotherapeutic agents including forms of antibodies such as omalizumab). be done.

Insect-Induced Allergy In some embodiments, the T _H2 -mediated condition includes insect-induced allergy and the additional therapeutic agent includes agents that can be used to treat insect-induced allergy. Such agents include antihistamines.

Drug Allergy In some embodiments, the T _H2 -mediated condition includes drug allergy and the additional therapeutic agent includes an agent that can be used to treat drug allergy. Such agents include antihistamines (eg, diphenhydramine) and corticosteroids, individually or in combination.

Anaphylaxis In some embodiments, the T _H 2-mediated condition includes anaphylaxis and the additional therapeutic agent includes agents that can be used to treat anaphylaxis. Such agents include foods, the same agents that can be used to treat allergies due to insect venoms, or drugs that can be used to treat anaphylaxis (eg, epinephrine).

Eosinophilia In some embodiments, the T _H2 -mediated condition includes eosinophilia (e.g., primary eosinophilia) and the additional therapeutic agent is eosinophilia. Agents that can be used for treatment are included. Such agents include corticosteroids such as prednisone.

For each of these T _H 2-mediated conditions, in some embodiments, pharmaceutical compositions of the present disclosure may be administered in addition to one or more of these provided additional therapeutic agents. For example, the pharmaceutical composition and an additional therapeutic agent may be co-administered.

Additional agents that may be useful in downregulatory pathways involved in T _H 2 cell activation include: mepolizumab, lebrikizumab, tralokinumab, GSK3772847, RG6149/AMG282, ANB020, OC000459, BI 671800, AZD1981, AS1517499. , YM-341619, AS1810722, SB010, resiquimod, imiquimod, and CYT003.

Administration In certain aspects, provided herein are methods of delivering a pharmaceutical composition containing Prevotella bacteria described herein to a subject. In some embodiments of the methods provided herein, the composition is administered with administration of an additional therapeutic agent (eg, an anti-inflammatory agent). In some embodiments, the Prevotella bacterium is co-formulated with an additional therapeutic agent in the pharmaceutical composition. In some embodiments, the Prevotella bacterium (eg, pharmaceutical composition thereof) is co-administered with an additional therapeutic agent. In some embodiments, the additional therapeutic agent is administered (eg, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 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 ago, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , or 14 days prior). In some embodiments, the additional therapeutic agent is administered (eg, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 1, 2, 3, 4, 5, 6, 7, 8, 9, After 10, 15, 20, 25, 30, 35, 40, 45, 50, or 55 minutes, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, After 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 hours, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , or 14 days later). In some embodiments, the same delivery modality is used to deliver both the Prevotella bacterium (eg, pharmaceutical composition thereof) and the additional therapeutic agent. In some embodiments, different modes of delivery are used to deliver the Prevotella bacterium (eg, pharmaceutical composition thereof) and the additional therapeutic agent. For example, in some embodiments, Prevotella bacteria (eg, pharmaceutical compositions thereof) are administered orally and the additional therapeutic agent is administered by injection (eg, intravenous and/or intramuscular injection).

In certain embodiments, the pharmaceutical compositions and dosage forms described herein may be administered with any other conventional treatment. This treatment may be applied as needed and/or indicated, and the treatment may be prior to, concurrently with, or after administration of the pharmaceutical compositions and dosage forms described herein. It can happen.

Dosage regimens can be any of a variety of methods and amounts, and can be determined by the skilled artisan according to known clinical factors. As is known in the medical arts, the dosage for any one patient can depend on many factors, such as the subject's species, size, body surface area, age, sex, immune competence, and overall It may depend on the particular health condition, the particular organism administered, the duration and route of administration, the type and stage of the disease, and other compounds (eg, co-administered drugs). In addition to the above factors, such levels may be influenced by the infectivity of the microorganism and the nature of the microorganism, as can be determined by one skilled in the art. The dosage of the pharmaceutical compositions described herein may be appropriately set or adjusted according to dosage form, route of administration, degree or stage of condition, and the like. For example, typical effective doses of drugs are 0.01 mg/kg body weight/day to 1000 mg/kg body weight/day, 0.1 mg/kg body weight/day to 1000 mg/kg body weight/day, 0.5 mg/kg body weight/day It can range from 500 mg/kg body weight/day, 1 mg/kg body weight/day to 100 mg/kg body weight/day, or 5 mg/kg body weight/day to 50 mg/kg body weight/day. This effective dose is , 500, or 1000 mg/kg body weight/day, or more, but this dose is not limited thereto.

In some embodiments, the dose administered to a subject is to prevent the condition, to delay the onset of the condition, to slow or stop the progression of the condition, or to prevent the recurrence of the condition. is sufficient to prevent Those skilled in the art will recognize that dosages will depend on various factors, such as the strength of the particular compound used and the age, species, condition, and 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 and desired physiological effects that may accompany administration of the particular compound. would

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. Routine and conventional means of effective dosing and treatment protocols, e.g., by starting with low doses in experimental animals, then increasing doses while monitoring efficacy, and then systematically varying the dosing regimen. can be determined by Generally, experimental animals are used to determine the maximum tolerated dose (“MTD”) of bioactive agent per kilogram of body weight. Those skilled in the art routinely extrapolate dosages for efficacy while avoiding toxicity in other species, such as humans.

In accordance with the above, in therapeutic applications, the dosage of an active agent to be used in accordance with the present invention will depend on the active agent, the age, weight, and clinical condition of the recipient patient, and the treatment, among other factors affecting the selected dosage. Varies depending on the experience and judgment of the clinician or professional administering the treatment. In general, the dose should be sufficient to cause a delay in progression of the condition, and preferably to cause regression.

Separate administrations can include any number of two or more administrations (doses), such as 2, 3, 4, 5, or 6 administrations. One of ordinary skill in the art can determine the number of doses, or The desirability of performing this administration can be readily determined. In some embodiments, the dose is at least , 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days, or 1, 2, 3, or 4 weeks apart. Thus, the methods provided herein include methods of administering one or more administrations of bacteria to a subject, wherein the number of administrations is monitored by the subject, and based on the results of this monitoring, one or more Decisions can be made by determining whether to administer multiple additional doses. The decision whether to administer one or more additional doses depends on various monitoring results, such as, but not limited to, the subject's anti-bacterial antibody titer, the subject's overall health, and/or the subject's weight. ).

Intervals between administrations can be of any of a variety of durations. The interval between administrations can be as described with respect to the number of administrations, the time period for the subject to mount an immune response, and/or the time period for the subject to clear the bacteria from normal tissue or from the gut, and the monitoring step. It can be a function of any of a variety of factors, including: In one example, the time period can be a function of the time period for the subject to mount an immune response, e.g., the time period can be greater than the time period for the subject to mount an immune response, e.g., greater than about a week, about may be greater than 10 days, greater than about 2 weeks, or greater than about 1 month, and in another example, the period of time may be less than the period for the subject to mount an immune response, e.g., less than about 1 week, about 10 It can be less than a day, 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 the subject to clear bacteria from normal tissue or from the intestine, e.g., the time period exceeds the time period for the subject to clear bacteria from normal tissue or from the intestine. for example, greater than about 1 day, greater than about 2 days, greater than about 3 days, greater than about 5 days, or greater than about 1 week.

In some embodiments, delivery of an additional therapeutic agent in combination with a Prevotella bacterium (e.g., a pharmaceutical composition thereof) described herein reduces side effects and/or provides additional treatment. The efficacy of the drug is improved.

An effective dose of an additional therapeutic agent, as described herein, is one that achieves the desired therapeutic response for a particular patient (e.g., subject), composition, and mode of administration with minimal toxicity to the patient. It is the amount of therapeutic agent effective to Effective dosage levels can be determined using the methods described herein and depend on various pharmacokinetic factors such as activity of the particular composition administered, route of administration, duration of administration, the excretion rate of the particular compound employed, the duration of treatment, other drugs, compounds and/or substances used in combination with the particular composition employed, the age, sex, weight, condition of the patient being treated, general health and previous medical history, and similar factors known in the medical arts). Generally, an effective dose of additional therapy will be that amount of therapeutic agent that is the lowest dose effective to produce a therapeutic effect. Such effective doses will generally depend on the factors explained above.

Toxicity of additional therapy refers to the level of side effects experienced by a subject during and after treatment. Adverse events associated with treatment toxicity include, but are not limited to: abdominal pain, hyperacidity, acid regurgitation, allergic reactions, hair loss, anaphylaxis, anemia, anxiety, anorexia, arthralgia, asthenia, movement. ataxia, azotemia, imbalance, bone pain, bleeding, blood clots, hypotension, hypertension, dyspnea, bronchitis, contusion, low white blood cell count, low red blood cell count, low platelet count, cardiotoxicity, cystitis, Hemorrhagic cystitis, arrhythmia, valvular heart disease, cardiomyopathy, coronary artery disease, cataract, central nervous system toxicity, cognitive impairment, confusion, conjunctivitis, constipation, cough, muscle spasm, cystitis, deep vein thrombosis, dehydration, depression, Diarrhea, dizziness, dry mouth, dry skin, indigestion, dyspnea, edema, electrolyte imbalance, esophagitis, fatigue, infertility, fever, flatulence, flushing, gastric reflux, gastroesophageal reflux disease, genital pain, granulocytes hypoplasia, gynecomastia, glaucoma, hair loss, hand-foot syndrome, headache, deafness, heart failure, heart palpitations, heartburn, hematoma, hemorrhagic cystitis, hepatotoxicity, hyperamylaseemia, hypercalcemia, hyperchloremia hyperglycemia, hyperkalemia, hyperlipaseemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hyperpigmentation, hypertriglyceridemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypochloremia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, erectile dysfunction, infection, injection site reaction, insomnia, iron deficiency, Pruritus, arthralgia, renal failure, leukopenia, liver dysfunction, memory loss, menopause, sore mouth, mucositis, myalgia, myalgia, myelosuppression, myocarditis, neutropenic fever, nausea, Nephrotoxicity, neutropenia, nosebleed, numbness, ototoxicity, pain, palmoplantar paresthesia, pancytopenia, pericarditis, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pneumonia, intermittent Qualitative pneumonia, proteinuria, pulmonary embolism, 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 benefit to the patient achieved through the treatment outweighs the adverse events experienced by the patient resulting from the treatment.

In some embodiments, the condition is treated by administration of Prevotella bacteria (eg, pharmaceutical compositions thereof).

As described herein, the condition to be treated can include T _H2 -mediated conditions and can include, for example, atopic dermatitis and/or food allergy.

Example 1: Effect of Prevotella histicola in a model of contact hypersensitivity using FITC Exposure of the skin to the antigen may cause, for example, a form of skin allergy (e.g., dermatitis, or atopic dermatitis, or eczema). and/or in the form of food allergy, an allergic reaction to this antigen may be triggered over time (eg Han et al. The topic 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/all.13404;Martel et al.Translational animal models of topical dermatitis for preclinical studies.Yale J.Biol.Med.2017.September;90(3):389-402; J. Invest. Dermatol. 2009. Jan: 129(1): 31-40. Doi 10.1038/jid.2008.106).

The effect of Prevotella histicola strain B 50329 was studied in a contact hypersensitivity model using fluorescein isothiocyanate (FITC) (see, for example, 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).

Prevotella histicola strain B 50329 was administered by oral gavage and various readouts were used to analyze the effect of Prevotella histicola on inflammation.

This study was carried out using microorganisms reconstituted from powder (eg powder in lyophilized form). Sucrose was used as the vehicle for reconstitution.

One vial of Prevotella histicola strain B 50329 and one vial of anaerobic sucrose were retrieved from the refrigerator by daily oral gavage. Appropriate bacterial solutions were prepared in sterile tubes using anaerobic sucrose. As an example, 800 ul of sucrose was added to 80 mg of Prevotella histicola strain B 50329. To ensure proper resuspension, the vial of resuspended powder was vortexed to keep powder from sticking to the vial. Mice were gavaged with resuspended powder in a volume of 100 μl per mouse immediately after vortexing (before powder settling) and residual powder mixture was discarded (freshly prepared each time). diluent must be used). Negative control mice were gavaged with 100 μl vehicle per day.

Hypersensitivity study protocol using FITC:
Mice were purchased from Taconic and acclimated to the animal facility for at least one week prior to initiation of experiments. Mice were housed with 5 animals (or less) per cage, each cage constituting a different treatment group.

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

On day 1, a solution of 0.5% FITC (w/v) was dissolved in adjuvant (diptyl phthalate (DBP)) and acetone (1:1). To prepare 0.5% FITC, 250 mg of FITC was dissolved in 25 ml of acetone. When completely dissolved, 25 ml of DBP was added and mixed by vortexing.

On days 1 and 2, mice were sensitized by pipetting μl of 0.5% FITC solution onto the back. Anaerobic sucrose served as a negative control. Dexamethasone served as a positive control (a dexamethasone stock solution was prepared by resuspending 25 mg of dexamethasone (Sigma) in 1.6 ml of 96% ethanol).

On days 1-6, mice were gavaged with vehicle (negative control, group 1) or Prevotella histicola strain B 50329 (group 3), or dexamethasone (positive) according to the study design described below. Controls, group 2) were injected intraperitoneally (ip).

daily oral gavage (groups 1 and 3) and i. p. In addition to the injection (group 2), on day 6, mice received a FITC challenge as follows: On day 6, each mouse was anesthetized with isoflurane and baseline left ear measurements were taken using calipers. A value was obtained and then the left ear was applied with 20 μl of 0.5% FITC solution (20 μl of 0.5% FITC (w/v) DBP:acetone (1.1)) (“ear challenge” or "FITC Challenge").

On day 7, calipers were used to obtain measurements at 8 hours after ear challenge. Mice were euthanized and ears were harvested for downstream mRNA analysis using the TaqMan RNA-to-CT 1-Step Kit (Applied Biosystems, ThermoFisher Scientific catalog number 4392653) according to the manufacturer's instructions.

Results are shown in FIGS. 1A and 1B.

Oral administration of Prevotella histicola strain B 50329 (labeled "Prevotella histicola" in FIGS. 1A-1B) significantly increased ear swelling 8 hours after FITC ear challenge. decreased (Fig. 1A).

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 ear (Fig. 1B).

Example 2: Effect of Prevotella histicola in a contact hypersensitivity model using FITC strain 1 and strain 2), strain 1 being a strain of Prevotella species other than histicola and strain 2 being a strain of a different genus than Prevotella.

On day 0, mice were anesthetized with isoflurane and their backs shaved as described in Example 1. On days 1 and 2, mice were sensitized by pipetting 400 μl of 0.5% FITC solution onto the back. On days 1-6, mice were orally gavaged with vehicle (sucrose) or bacterial strains to be tested, or intraperitoneally (ip) injected with dexamethasone (positive control).

On day 6, each mouse was anesthetized with isoflurane and baseline left ear measurements were obtained using calipers as described in Example 1. Mice were then FITC challenged with 20 μl of 0.5% FITC solution applied to the left ear.

On day 7, mice were euthanized exactly 8 hours post-challenge and post-challenge ear measurements were obtained using calipers.

The results are shown in Table 2. Oral administration of Prevotella histicola strain B 50329 (labeled "Prevotella histicola" in Figure 2) significantly reduced ear swelling 8 hours after FITC challenge, although , two other bacterial strains (number 1 and strain 2) did not decrease (Fig. 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, although Prevotella histicola histicola) strain B 50329 and strain 2 (a strain in a different genus than Prevotella) was statistically significant.

Example 3: Effect of Prevotella histicola in the MC903 model of dermatitis-associated food allergy to the egg white protein ovalbumin (OVA). of bacterial strains were evaluated.

MC903, a vitamin D3 analogue, induces inflammation and has been used in models of atopic dermatitis (see, eg, Hussain et al. Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of all foods. ２０１７．Ａｍｅｒｉｃａｎ Ａｃａｄｅｍｙ ｏｆ Ａｌｌｅｒｇｙ，Ａｓｔｈｍａ＆Ｉｍｍｕｎｏｌ．ｈｔｔｐ：／／ｄｘ．ｄｏｉ．ｏｒｇ／１０．１０１６／ｊ．ｊａｃｉ．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).

MC903 can be used to skin sensitize mice to antigens of interest, resulting in skin sensitization typified by the production of TCLP and IL-4 (see, for example, Noti et al. Exposure to food allergens through inflamed skin promotes intestinal (see 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 (eg, OVA) to test can be obtained from vendors such as Invivogen or Sigma.

Materials and Methods Female BALB/c mice (6-8 weeks old) were purchased from Taconic Farms. Animals were housed under specific pathogen-free conditions in an animal facility (5 mice or less than 5 mice per cage) and all experiments were performed by the Institutional Animal Care and Use Committee (IACUC). Conducted under approved protocols and guidelines. Mice were acclimated in the animal facility for one week prior to the start of this experiment. They were fed PicoLab Rodent Diet 20 and autoclaved water ad libitum via sipper bottles and checked daily.

To induce a mouse model that mimics egg food allergy, mice were exposed to MC903 (Tocris) and 100 μg ovalbumin (OVA) daily for 14 consecutive days (days 1-14). 45 μM MC903 in 20 μL of 100% ethanol was applied to one ear by pipette and once the ear was dry, 100 μg of OVA in PBS was applied. Ears of the vehicle control group were smeared with 20 μL of ethanol.

For daily gavage treatment (days 1-17), negative control mice received vehicle (lyophilized sucrose) and positive control mice received tofacitinib (100 ul/mouse in 0.5% methylcellulose). 20 mg/kg (p.o.); Tocris). One group of mice was dosed daily with 10 mg of Prevotella histicola strain B 50329 (3.13E+09 TCC/dose) and other groups were dosed with strain A (1.23E+10 TCC/dose) or strain B ( 7.83E+09 TCC/dose) either (Prevotella histicola strain B Bacterial strain that is not 50329 - strain A is a strain in a different genus than Prevotella, strain B is a strain of Prevotella 10 mg of Histicola (which was another strain of Prevotella histicola) was administered. On day 15, mice were challenged by oral gavage (p.o., also called intragastric (ig)) with 50 mg OVA.

On day 17.5, mice were given a second oral challenge with 50 mg OVA. After this second challenge, ear inflammation was measured using calipers.

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 "P. histicola" in Figures 3B-3D) significantly reduced ear inflammation compared to the negative control group. did.

On day 18, 12 hours after the second OVA challenge, mice were euthanized. Blood (for serum) and tissues (eg, spleen, draining cervical lymph nodes, mesenteric lymph nodes, and ears) were collected and processed ex vivo.

Chondrex, Inc. Sera were analyzed by ELISA for anti-OVA IgG1, anti-OVA IgE using the Mouse Anti-OVA IgG1 Antibody Assay Kit (Cat#3013) and Mouse Anti-OVA IgE Antibody Assay Kit (Cat#3010). The results are shown in Figure 3C.

Ears were homogenized and cytokine detection was performed. Spleens, mesenteric lymph nodes (mLN), and cervical lymph nodes (cLN) were analyzed for cytokine expression after in vitro PMA stimulation and supernatant collection. A single cell suspension of the tissue was prepared, counted, plated at 200,000 cells/well, and resuspended in PMA/Ionomycin (eBiosciences Cell Stimulation cocktail Cat #00-4975) for 48 hours according to the manufacturer's instructions. stimulated. Supernatants were harvested and used in a downstream multiplex ELISA to determine cytokine levels using the Meso Scale Discovery (MSD) kit (catalog number K15068L-2). Similarly, ears were isolated in 250 ul of T-PER buffer (Thermo Scientific Cat.#78510) containing Halt Protease (Thermo Scientific Cat.#78444) and protein concentration was determined using a BCA kit (Thermo Scientific Cat.#23227). was quantified. Using 100 ug of protein, cytokine levels were quantified using the MSD kit (catalog number K15068L-2). The results are shown in Figure 3D.

Example 4: Effect of Prevotella histicola in MC903 Model of Type 2 (Th2) Immune Response in Food Allergy to OVA and Complete Peanut Protein (CPE) Induction Mouse Models Mimicking Egg Food Allergy and Peanut Allergy To do so, mice were sensitized to food allergens as described in Example 3 and depicted in FIG. 4A.

MC903 was prepared in EtOH and applied daily as indicated (days 1-14).

Some mice were exposed to MC903 and 100 ug OVA in PBS daily for 14 consecutive days. Other mice were exposed to MC903 and 100 ug complete peanut protein (CPE) daily for 14 consecutive days. In addition to antigen (e.g., OVA or CPE) application, mice were treated with sucrose vehicle (negative control), tofacitinib (positive control), bacterial strain A (10 mg/dose), or Prevotella histicola strain B 50329. (10 mg/dose) was administered by oral gavage. Strain A is of a different genus than Prevotella.

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

On day 17.5, mice were challenged a second time by oral gavage with either 50 mg OVA or 50 mg complete peanut powder (CPE).

Ear thickness was measured on day 18, 12 hours after the final antigen challenge. Mice were euthanized and serum and tissues were collected as described in Example 3.

As shown in Figure 4B, Prevotella histicola strain B 50329 (labeled "P. histicola" in Figures 4B-4D) is associated with the OVA group and peanut allergy ( CPE) groups significantly reduced ear inflammation compared to the vehicle control group. Antibody assays (anti-OVA IgG1 and anti-OVA IgE) were performed as described in Example 3 and the results are shown in Figure 4C. Cytokine analysis was performed as described in Example 3 and is shown in Figure 4D. Ear RNA was measured as described in Example 1 and the results are shown in FIG. 4E.

Example 5: Atopic Dermatitis and Anaphylaxis with MC903 As described in Example 3 and Mice were sensitized to food allergens as depicted in FIG.

MC903 was prepared in EtOH and applied daily as indicated (days 1-14).

Some mice were exposed to MC903 and 100 ug CPE in PBS daily for up to 30 consecutive days. In addition to application of a model antigen (e.g. CPE), mice were given sucrose vehicle (negative control), tofacitinib (positive control; 100 μl po daily), bacterial strain A (10 mg/dose), or Prevotella histicola. Strain B 50329 (10 mg/dose) or 200 μg/mouse of anti-IL-4 (ip days 3, 6, 9, and 12; BioXcell) were administered by oral gavage (days 1-17, or 1 to 30 days).

On day 30, mice were dosed with 500ug CPE i. p. challenge and observed for anaphylaxis. Thirty minutes after CPE challenge, body temperature was measured using a rectal thermometer.

On day 31, mice were sacrificed and ear inflammation was measured. Spleen, ear, and lymphoid tissue cytokines were analyzed using the methods described in Examples 1 and 3.

Example 6: Tape Stripped Peanut Allergy Model As explained above, various animal models exist for studying food allergy. Some of these models induce allergen (e.g., antigen) sensitization 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 Kanagaratham et al.Experimental models for studying food allergy.Cell Mol Gastroenterol Hepatol.2018.6(3):356-369.e1.Doi:10.1016/j.j.cmgh.2010.05. see). In some models, skin barrier defects are induced by repeated stripping of tape from the skin after shaving the fur, and allergens are applied to the resulting damaged skin. At some point this "skin sensitization" to the allergen is followed by an intragastric challenge to the allergen. For example, as shown in Figure 6A, mice were subjected to tape stripping and peanut antigen on either days 1, 2, and 3 (ear sensitization) or days 0, 3, and 6 (back sensitization). exposure can be used to sensitize the ear or back. Mice are tape-stripped on day 0 only for the ear-sensitized group and tape-stripped on days 0, 3, and 6 for the back-sensitized group. Mice can be challenged on day 21, immediately after which various readings such as, but not limited to, measurement of serum peanut-specific IgE, IgG1, and IgA, and total IgE, IgG1, and IgA, body temperature, anaphylaxis scoring, diarrhea scoring, and/or ex vivo restimulation of mesenteric lymph node (MLN) cells) and/or sacrificed to assess various cytokines (e.g., IL-4, IL-5). , and TSLP) can be evaluated. Alternatively, serum can be collected on day 35 (see Figure 6B), otherwise the study can be conducted over 65 days (see Figure 6C). Mice can be scored for anaphylaxis and diarrhea as shown in Tables 3 and 4, respectively.

Female BLAB/c mice were purchased from Taconic Farms and all experiments were performed under protocols and guidelines approved by the Institutional Animal Care and Use Committee (IACUC).

Mice were acclimated in the animal facility for one week prior to the start of this experiment. All mice were housed no more than 5 per cage in individually ventilated cages with standard bedding and enrichment. They were fed PicoLab Rodent Diet 20 and autoclaved water ad libitum via sipper bottles and checked daily.

Experimental Design Animal groups were divided as follows (5 mice/group):
1) naive mice (no sensitization, no peanut challenge);
2) naive mice (no sensitization, peanut challenge on day 21);
3) ear sensitization (sensitization on days 1, 2, and 3) (no challenge);
4) ear sensitization (sensitization on days 1, 2, and 3) (peanut challenge on day 21);
5) ear sensitization (sensitization on days 1, 2, and 3) (tofacitinib 20 mg/kg) (peanut challenge on day 21);
6) ear sensitization (sensitization on days 1, 2 and 3) (P. histicola 10 mg) (peanut challenge on day 21);
7) back sensitization (sensitized on days 0, 3, and 6) (no challenge);
8) back sensitization (sensitization on days 0, 3, and 6) (peanut challenge on day 21);
9) back sensitization (sensitization on days 0, 3, and 6) (tofacitinib 20 mg/kg) (peanut challenge on day 21);
and 10) back sensitization (sensitization on days 0, 3, and 6) (Prevotella histicola strain B 50329 10 mg) (peanut challenge on day 21).

On day 0, mice were individually anesthetized with isoflurane. For the ear sensitization group, tape stripping with cellophane tape from each mouse's ear was repeated (approximately 7-8 times). In the case of the back-sensitized group, the hair on the back was shaved and the tape was peeled off with cellophane tape (about 7-8 times).

For the ear sensitization group, mice underwent tape stripping on day 0. On days 1, 2 and 3, 25 μl of peanut protein solution (4 mg/ml peanut protein in PBS) was applied to both ears by cotton swab.

For the back sensitization group, on days 0, 3, and 6, mice were tape stripped and 100 μg of peanut protein was applied. Each time the sensitized area was covered with a new waterproof dressing.

For the Prevotella histicola strain B 50329 group, mice were gavaged with 10 mg of bacteria on days 1-21.

On day 21, mice from groups 2, 4, 5, 6, 8, and 9 were challenged with 100 mg peanut protein by oral gavage. Mice from all groups were cheek bled 1 hour after peanut protein challenge and subjected to total IgE, peanut-specific IgE, total IgG1, peanut-specific IgG1, total IgA, and peanut-specific IgA ELISAs (Chondrex, manufacturer according to the instructions).

Inflammation results are shown in FIG. 6D. For both ear and back groups, Prevotella histicola strain B 50329 (labeled "P. histicola" in Figures 6D-6I) reduced inflammation.

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

Total and peanut-specific serum IgE, IgG1, and IgA levels from 2 weeks post-challenge are shown in Figures 6G, 6H, and 6I, respectively.

Example 7: FITC-CHS Model Prevotella histicola strain B 50329 was tested in the FITC-CHS model as shown in Figure 7A. The dose tested was 4.69E+09 TCC.

On day 7, the effect of Prevotella histicola strain B 50329 on TH2 cytokines (IL-13, IL-4, IL-5, IL-31 and IL-33) was examined. As shown in FIG. 7B, Prevotella histicola strain B 50329 (labeled as "Prevotella histicola" in FIGS. 7B-7C) is associated with gastrointestinal draining mesenteric lymph nodes (gut). IL-13, IL-5, and IL-31 levels in the draining mesenteric lymph nodes were significantly reduced. Cytokine levels were determined by MSD and experiments were performed as described in Example 3. As shown in FIG. 7C, Prevotella histicola strain B 50329 treatment significantly reduced levels of IL-13 in ear-draining neck lymph nodes. Experiments were performed as described in Example 3.

This example demonstrates that Prevotella histicola strain B 50329 treatment increases T _H2 cytokine secretion in PMA/ionomycin ex vivo restimulated cells from gut-draining mesenteric and ear-draining cervical lymph nodes. A significant reduction has been demonstrated.

Example 8: Atopic Dermatitis Using MC903 As shown in Figure 8A, Prevotella histicola strain B 50329 was tested in an atopic dermatitis model using MC903.

For this experiment, mice were purchased from Taconic Labs and acclimated to the animal facility for one week prior to initiation of the experiment. Mice were housed 5 animals per cage in individually ventilated cages with standard bedding and enrichment. They were fed Standard Purina rodent diet (5001) and autoclaved water ad libitum and checked daily.

On day 1, mice were anesthetized and baseline ear measurements were obtained. The ears were then sensitized with 45 nM calcipitriol (MC903) while under anesthesia by pipetting a total of 20 uL of solution onto both the back and front of the ear. Ears were sensitized daily for 14 days.

On days 1-14, mice were gavaged QD daily with a dose of 4.69E+09 TCC of Prevotella histicola strain B 50329 or a positive control (tofacitinib).

Ear measurements were obtained throughout the study to follow changes in thickness over time, and on day 14, changes in ear thickness from baseline were determined.

On day 17, ex vivo experiments were performed.

Preparation protocol for MC903: 10 mg of calcipitriol powder was dissolved in 10 mL of 99% ethanol to make a 1 mg/mL stock. The stock was diluted with 99% ethanol to 0.01856 mg/mL. This diluted solution was aliquoted into routine light-tight tubes at -20°C.

Positive Control—Preparation of Tofacitinib: Tofacitinib was prepared in 0.5% (w/v) methylcellulose. Purified water was brought to a boil on a stirring/heating plate. An appropriate amount of powdered methylcellulose was weighed. Boiling water was stirred and powdered methylcellulose was added. Stirring was continued until the powder was incorporated into the water. The mixture was cooled to 4° C. overnight while stirring on a stir plate. A 50 mg stock of tofacitinib was resuspended in 0.5% MC (the mixture formed a suspension). Tofacitinib was administered p.p. at 100 uL per mouse. o. dosed.

result:
As shown in Figure 8B, Prevotella histicola strain B 50329 (labeled "Prevotella histicola" in Figures 8B-8E) treatment resulted in ear measurements over time (left Ear inflammation in atopic dermatitis with MC903 was reduced as determined by ear inflammation at day 14 (right panel) and at day 14 (right panel).

On day 17, the effect of Prevotella histicola strain B 50329 on TH2 cytokine transcript levels (Tslp, Il5, Il31, Il4, Ccl19, and Ccr4) in ear tissue was examined. As shown in FIG. 8C, Prevotella histicola strain B 50329 treatment readily reduced the levels of Il5, Il31, and Ccr4 transcripts in ear tissue as determined by qPCR.

On day 17, the effect of Prevotella histicola strain B 50329 on mast cell-associated gene transcript levels (Mcpt1) in the jejunum was examined. From the results in FIG. 8D, Prevotella histicola strain B 50329 significantly reduced Mcpt1 transcript levels in the jejunum of mice in an atopic dermatitis model using MC903, as determined by qPCR. is demonstrated.

On day 17, the effect of Prevotella histicola strain B 50329 on IL-10 levels in mesenteric lymph nodes and spleen was examined. Prevotella histicola strain B 50329 upon ex vivo restimulation with PMA/ionomycin in tissues isolated from atopic dermatitis with MC903, as determined by MSD, as shown in FIG. 8E. Treatment significantly elevated IL-10 levels in the mesenteric lymph nodes and spleens of mice. This experiment was performed as described in Example 3.

The results of this example demonstrate that ear inflammation in atopic dermatitis with MC903 was significantly reduced by Prevotella histicola strain B 50329 treatment compared to vehicle-treated mice. there is

Prevotella histicola strain B 50329 treatment showed a reduction of TH2 cytokine transcripts in ear tissue and mast cell-associated transcripts (Mcpt1) in the jejunum.

Prevotella histicola strain B 50329 treatment showed elevated levels of IL-10 in gut-draining mesenteric lymph nodes and splenocytes upon ex vivo restimulation with PMA/ionomycin.

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

EQUIVALENTS 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. deaf. Such equivalents are intended to be included in the scope of the appended claims.

Claims (235)

A method of treating or preventing a T _H2 -mediated condition in a subject, said method comprising administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria. 2. The method of claim 1, wherein said subject is a human subject. 2. At least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial content of said pharmaceutical composition is derived from Prevotella bacteria. Or the method of 2. The method of any one of claims 1-3, wherein said method treats said T _H 2-mediated condition. The method of any one of claims 1-4, wherein the T _H2 -mediated condition is asthma, atopic dermatitis, eosinophilic disease and/or allergy. 6. The method of claim 5, wherein the T _H2 -mediated condition is allergy, and wherein said allergy is food allergy, seasonal allergic rhinitis, and/or pet allergy. 6. The method of claim 5, wherein said T _H2 -mediated condition is atopic dermatitis. 6. The method of claim 5, wherein said T _H2 -mediated condition is food allergy. 9. The method of claim 8, wherein the food allergy is peanut allergy, milk allergy, chicken egg allergy, fish allergy, shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. 9. The method of claim 8, wherein said food allergy is peanut allergy. 9. The method of claim 8, wherein the food allergy is allergy to food antigens. 12. The method of claim 11, wherein the food antigen is a peanut antigen, milk antigen, chicken egg antigen, fish antigen, shellfish antigen, tree nut antigen, wheat antigen, or soybean antigen. 12. The method of claim 11, wherein said food antigen is a peanut antigen. 14. The method of any one of claims 1-13, wherein the method reduces interleukin (IL)-4 levels in the subject. 15. The method of claim 14, wherein said IL-4 level is IL-4 protein level or IL-4 mRNA level. 16. The method of any one of claims 1-15, wherein the method reduces interleukin (IL)-5 levels in the subject. 17. The method of claim 16, wherein said IL-5 level is IL-5 protein level or IL-5 mRNA level. 18. The method of any one of claims 1-17, wherein the method reduces interleukin (IL)-13 levels in the subject. 19. The method of claim 18, wherein said IL-13 level is IL-13 protein level or IL-13 mRNA level. 20. The method of any one of claims 1-19, wherein the method reduces interleukin (IL)-19 levels in the subject. 21. The method of claim 20, wherein said IL-19 level is IL-19 protein level or IL-19 mRNA level. 22. The method of any one of claims 1-21, wherein the method reduces interleukin (IL)-21 levels in the subject. 23. The method of claim 22, wherein said IL-21 level is IL-21 protein level or IL-21 mRNA level. 24. The method of any one of claims 1-23, wherein the method reduces interleukin (IL)-31 levels in the subject. 25. The method of claim 24, wherein said IL-31 level is IL-31 protein level or IL-31 mRNA level. 26. The method of any one of claims 1-25, wherein the method reduces interleukin (IL)-33 levels in the subject. 27. The method of claim 26, wherein said IL-33 level is IL-33 protein level or IL-33 mRNA level. 28. The method of any one of claims 1-27, wherein the method reduces thymic stromal lymphopoietin (TSLP) levels in the subject. 29. The method of claim 28, wherein said TSLP level is TSLP protein level or TSLP mRNA level. 30. The method of any one of claims 1-29, wherein the method reduces IgGl levels in the subject. 31. The method of claim 30, wherein said IgGl level is IgGl protein level or IgGl mRNA level. 32. The method of any one of claims 1-31, wherein the method reduces IgE levels in the subject. 33. The method of claim 32, wherein said IgE level is IgE protein level or IgE mRNA level. 34. The method of any one of claims 1-33, wherein the method reduces IgA levels in the subject. 35. The method of claim 34, wherein said IgA level is IgA protein level or IgA mRNA level. The Prevotella bacterium includes Prevotella albensis, Prevotella aminii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotellaブライアンティイ（Ｐｒｅｖｏｔｅｌｌａ ｂｒｙａｎｔｉｉ）、プレボテラ・ブッカエ（Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｅ）、プレボテラ・ブッカリス（Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｌｉｓ）、プレボテラ・コプリ（Ｐｒｅｖｏｔｅｌｌａ ｃｏｐｒｉ）、プレボテラ・デンタリス（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｌｉｓ）、プレボテラ・デンティコーラ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔｉｃｏｌａ）、プレボテラ・ディシエンス（Ｐｒｅｖｏｔｅｌｌａ ｄｉｓｉｅｎｓ）、プレボテラ・ヒスチコーラ（Ｐｒｅｖｏｔｅｌｌａ ｈｉｓｔｉｃｏｌａ）、プレボテラ・インターメディア（Ｐｒｅｖｏｔｅｌｌａ ｉｎｔｅｒｍｅｄｉａ）、プレボテラ・マクローサ（Ｐｒｅｖｏｔｅｌｌａ ｍａｃｕｌｏｓａ）、プレボテラ・マルシイ（Ｐｒｅｖｏｔｅｌｌａ ｍａｒｓｈｉｉ）、プレボテラ・メラニノジェニカ（Ｐｒｅｖｏｔｅｌｌａ ｍｅｌａｎｉｎｏｇｅｎｉｃａ）、プレボテラ・マイカンス（ Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella aurorolum, Prevotella aurorolum ( Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni ｊｅｊｕｎｉ）、プレボテラ・オーランティアカ（Ｐｒｅｖｏｔｅｌｌａ ａｕｒａｎｔｉａｃａ）、プレボテラ・バーロニアエ（Ｐｒｅｖｏｔｅｌｌａ ｂａｒｏｎｉａｅ）、プレボテラ・コロランス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｌｏｒａｎｓ）、プレボテラ・コルポリス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｒｐｏｒｉｓ）、プレボテラ・デンタシニ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｓｉｎｉ）、プレボテラ・エノエカ（Ｐｒｅｖｏｔｅｌｌａ ｅｎｏｅｃａ）、プレボテラ・ファルセニイ（Ｐｒｅｖｏｔｅｌｌａ ｆａｌｓｅｎｉｉ）、プレボテラ・フスカ（Ｐｒｅｖｏｔｅｌｌａ ｆｕｓｃａ）、プレボテラ・ヘパリノリティカ（Ｐｒｅｖｏｔｅｌｌａ ｈｅｐａｒｉｎｏｌｙｔｉｃａ）、プレボテラ・ロエッシェイイ（Ｐｒｅｖｏｔｅｌｌａ ｌｏｅｓｃｈｅｉｉ）、プレボテラ・マルチサッカリボラックス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｓａｃｃｈａｒｉｖｏｒａｘ）、プレボテラ・ナンセイエンシス（Ｐｒｅｖｏｔｅｌｌａ ｎａｎｃｅｉｅｎｓｉｓ）、プレボテラ・オリザエ（Ｐｒｅｖｏｔｅｌｌａ ｏｒｙｚａｅ）、プレボテラ・パルディビエンス（Ｐｒｅｖｏｔｅｌｌａ ｐａｌｕｄｉｖｉｖｅｎｓ）、プレボテラ・プレウリチディス（Ｐｒｅｖｏｔｅｌｌａ ｐｌｅｕｒｉｔｉｄｉｓ）、プレボテラ・ルミニコーラ（Ｐｒｅｖｏｔｅｌｌａ ｒｕｍｉｎｉｃｏｌａ）、プレボテラ・サッカロリティカ（Ｐｒｅｖｏｔｅｌｌａ ｓａｃｃｈａｒｏｌｙｔｉｃａ ), Prevotella scopos, Prevotella shahii, Prevotella zooogleoformans, and/or Prevotella veroralis The method according to item 1. 37. The method of claim 36, wherein the Prevotella bacterium is Prevotella histicola. The Prevotella bacterium exhibits at least 95% genomic sequence identity, 16S sequence identity, and/or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). 38. The method of any one of claims 1-37, which is a strain comprising. The Prevotella bacterium exhibits at least 99% genomic sequence identity, 16S sequence identity, and/or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). 39. The method of claim 38, which is a strain comprising. 40. The method of claim 39, wherein the Prevotella bacterium is Prevotella strain B 50329 (NRRL Accession No. B 50329). 41. The method of any one of claims 1-40, wherein the Prevotella bacterium is a strain of Prevotella bacterium comprising one or more of the proteins listed in Table 1. 42. The method of any one of claims 1-41, wherein the Prevotella bacterium is a strain of Prevotella that is substantially free of the proteins listed in Table 2. 43. The method of any one of claims 1-42, wherein the pharmaceutical composition comprises live, killed, or attenuated bacteria. 42. The Prevotella bacterium has been gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated and/or oxygen-sparged, claims 1-42 The method according to any one of . 45. The method of claim 44, wherein the Prevotella bacteria are heat inactivated at 50<0>C for 2 hours or at 90<0>C for 2 hours. 45. The method of claim 44, wherein the Prevotella bacteria are oxygen sparged at 0.1 vvm for 2 hours. 47. The method of any one of claims 1-46, wherein the Prevotella bacteria are freeze-dried Prevotella bacteria. 48. The method of claim 47, wherein said composition further comprises a pharmaceutically acceptable excipient. 49. The method of any one of claims 1-48, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species. 49. The method of any one of claims 1-48, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. 49. The method of any one of claims 1-48, wherein the Prevotella bacteria in the pharmaceutical composition are from different species. 50. The method of any one of claims 1-49, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. 53. The method of any one of claims 1-52, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent. 54. The method of claim 53, wherein said additional therapeutic agent is an anti-inflammatory agent. 55. The method of any one of claims 1-54, wherein the pharmaceutical composition is formulated as a solid dosage form. 56. The method of Claim 55, wherein the solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof. 57. The method of claim 55 or 56, wherein said solid dosage form further comprises a pharmaceutically acceptable excipient. 58. The method of any one of claims 55-57, wherein the solid dosage form comprises an enteric coating. 59. The method of any one of claims 55-58, wherein the solid dosage form is formulated for oral administration. 55. The method of any one of claims 1-54, wherein the pharmaceutical composition is formulated as a suspension. 61. The method of claim 60, wherein said suspension is formulated for oral administration. 62. The method of claim 60 or 61, wherein the suspending agent comprises PBS and optionally sucrose or glucose. 61. The method of claim 60, wherein said suspension is formulated for intravenous administration. 61. The method of claim 60, wherein said suspension is formulated for intraperitoneal administration. 65. The method of claim 63 or 64, wherein the suspending agent comprises PBS. 61. The method of claim 60, wherein said pharmaceutical composition is administered intravenously. 61. The method of claim 60, wherein the pharmaceutical composition is administered by injection, for example by subcutaneous, intradermal or intraperitoneal injection. 68. The method of any one of claims 60-67, wherein the suspension further comprises a pharmaceutically acceptable additive. The method of any one of claims 60-68, wherein said suspending agent further comprises a buffer. 70. The method of claim 69, wherein said buffer is PBS. 71. The method of any one of claims 1-70, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents. 72. The method of Claim 71, wherein said one or more additional therapeutic agents is one or more anti-inflammatory agents. The method of any one of claims 1-62 or 68-72, wherein said pharmaceutical composition is administered orally. 74. The method of any one of claims 1-73, wherein the pharmaceutical composition comprises from about 5 mg to about 900 mg total protein as determined by the Bradford assay or the BCA assay. 75. The method of any one of claims 1-74, wherein the pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by the Bradford assay or the BCA assay. 76. The method of any one of claims 1-75, further comprising administering an additional therapeutic agent to the subject. 77. The method of claim 76, wherein said additional therapeutic agent is an anti-inflammatory agent. 77. The method of Claim 76, wherein said additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukotriene receptor antagonist, an antibody, or a combination thereof. 78. The method of claim 76 or 77, wherein said pharmaceutical composition comprises said additional therapeutic agent. 77. The method of claim 76, wherein said additional therapeutic agent is an antibiotic agent. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria for use in treating or preventing a T _H2 -mediated condition in a subject. 82. The pharmaceutical composition of claim 81, wherein said subject is a human subject. 81. At least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial content of said pharmaceutical composition is derived from Prevotella bacteria. Or the pharmaceutical composition according to 82. 84. The pharmaceutical composition of any one of claims 81-83, wherein said pharmaceutical composition treats said T _H 2-mediated condition. The pharmaceutical composition according to any one of claims 81-84, wherein said T _H2 -mediated condition is asthma, atopic dermatitis, eosinophilic disease and/or allergy. 86. The pharmaceutical composition of claim 85, wherein the T _H2 -mediated condition is allergy, and wherein said allergy is food allergy, seasonal allergic rhinitis, and/or pet allergy. 86. The pharmaceutical composition of claim 85, wherein said T _H2 -mediated condition is atopic dermatitis. 86. The pharmaceutical composition of claim 85, wherein said T _H2 -mediated condition is food allergy. 89. The pharmaceutical composition of claim 88, wherein the food allergy is peanut allergy, milk allergy, chicken egg allergy, fish allergy, shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. 89. The pharmaceutical composition of claim 88, wherein said food allergy is peanut allergy. 89. The pharmaceutical composition of claim 88, wherein food allergy is allergy to food antigens. 92. The pharmaceutical composition of claim 91, wherein said food antigen is a peanut antigen, milk antigen, chicken egg antigen, fish antigen, shellfish antigen, tree nut antigen, wheat antigen, or soybean antigen. 92. The pharmaceutical composition of Claim 91, wherein said food antigen is a peanut antigen. 94. The pharmaceutical composition of any one of claims 81-93, wherein administration of said pharmaceutical composition reduces interleukin (IL)-4 levels in said subject. 95. The pharmaceutical composition of claim 94, wherein said IL-4 level is IL-4 protein level or IL-4 mRNA level. 96. The pharmaceutical composition of any one of claims 81-95, wherein administration of said pharmaceutical composition reduces interleukin (IL)-5 levels in said subject. 97. The pharmaceutical composition of claim 96, wherein said IL-5 level is IL-5 protein level or IL-5 mRNA level. 98. The pharmaceutical composition of any one of claims 81-97, wherein administration of said pharmaceutical composition reduces interleukin (IL)-13 levels in said subject. 99. The pharmaceutical composition of claim 98, wherein said IL-13 level is IL-13 protein level or IL-13 mRNA level. 99. The pharmaceutical composition of any one of claims 81-99, wherein administration of said pharmaceutical composition reduces interleukin (IL)-19 levels in said subject. 101. The pharmaceutical composition of claim 100, wherein said IL-19 level is IL-19 protein level or IL-19 mRNA level. 102. The pharmaceutical composition of any one of claims 81-101, wherein administration of said pharmaceutical composition reduces interleukin (IL)-21 levels in said subject. 103. The pharmaceutical composition of claim 102, wherein said IL-21 level is IL-21 protein level or IL-21 mRNA level. 104. The pharmaceutical composition of any one of claims 81-103, wherein administration of said pharmaceutical composition reduces interleukin (IL)-31 levels in said subject. 105. The pharmaceutical composition of claim 104, wherein said IL-31 level is IL-31 protein level or IL-31 mRNA level. 106. The pharmaceutical composition of any one of claims 81-105, wherein administration of said pharmaceutical composition reduces interleukin (IL)-33 levels in said subject. 107. The pharmaceutical composition of claim 106, wherein said IL-33 level is IL-33 protein level or IL-4 mRNA level. 108. The pharmaceutical composition of any one of claims 81-107, wherein administration of said pharmaceutical composition reduces thymic stromal lymphopoietin (TSLP) levels in said subject. 109. The pharmaceutical composition according to claim 108, wherein said TSLP level is TSLP protein level or TSLP mRNA level. 110. The pharmaceutical composition of any one of claims 81-109, wherein administration of said pharmaceutical composition reduces IgGl levels in said subject. 111. The pharmaceutical composition of claim 110, wherein said IgGl level is IgGl protein level or IgGl mRNA level. 112. The pharmaceutical composition of any one of claims 81-111, wherein administration of said pharmaceutical composition reduces IgE levels in said subject. 113. The pharmaceutical composition of claim 112, wherein said IgE level is IgE protein level or IgE mRNA level. The pharmaceutical composition of any one of claims 81-113, wherein administration of said pharmaceutical composition reduces IgA levels in said subject. 115. The pharmaceutical composition of claim 114, wherein said IgA level is IgA protein level or IgA mRNA level. The Prevotella bacterium includes Prevotella albensis, Prevotella aminii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotellaブライアンティイ（Ｐｒｅｖｏｔｅｌｌａ ｂｒｙａｎｔｉｉ）、プレボテラ・ブッカエ（Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｅ）、プレボテラ・ブッカリス（Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｌｉｓ）、プレボテラ・コプリ（Ｐｒｅｖｏｔｅｌｌａ ｃｏｐｒｉ）、プレボテラ・デンタリス（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｌｉｓ）、プレボテラ・デンティコーラ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔｉｃｏｌａ）、プレボテラ・ディシエンス（Ｐｒｅｖｏｔｅｌｌａ ｄｉｓｉｅｎｓ）、プレボテラ・ヒスチコーラ（Ｐｒｅｖｏｔｅｌｌａ ｈｉｓｔｉｃｏｌａ）、プレボテラ・インターメディア（Ｐｒｅｖｏｔｅｌｌａ ｉｎｔｅｒｍｅｄｉａ）、プレボテラ・マクローサ（Ｐｒｅｖｏｔｅｌｌａ ｍａｃｕｌｏｓａ）、プレボテラ・マルシイ（Ｐｒｅｖｏｔｅｌｌａ ｍａｒｓｈｉｉ）、プレボテラ・メラニノジェニカ（Ｐｒｅｖｏｔｅｌｌａ ｍｅｌａｎｉｎｏｇｅｎｉｃａ）、プレボテラ・マイカンス（ Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella aurorolum, Prevotella aurorolum ( Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni ｊｅｊｕｎｉ）、プレボテラ・オーランティアカ（Ｐｒｅｖｏｔｅｌｌａ ａｕｒａｎｔｉａｃａ）、プレボテラ・バーロニアエ（Ｐｒｅｖｏｔｅｌｌａ ｂａｒｏｎｉａｅ）、プレボテラ・コロランス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｌｏｒａｎｓ）、プレボテラ・コルポリス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｒｐｏｒｉｓ）、プレボテラ・デンタシニ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｓｉｎｉ）、プレボテラ・エノエカ（Ｐｒｅｖｏｔｅｌｌａ ｅｎｏｅｃａ）、プレボテラ・ファルセニイ（Ｐｒｅｖｏｔｅｌｌａ ｆａｌｓｅｎｉｉ）、プレボテラ・フスカ（Ｐｒｅｖｏｔｅｌｌａ ｆｕｓｃａ）、プレボテラ・ヘパリノリティカ（Ｐｒｅｖｏｔｅｌｌａ ｈｅｐａｒｉｎｏｌｙｔｉｃａ）、プレボテラ・ロエッシェイイ（Ｐｒｅｖｏｔｅｌｌａ ｌｏｅｓｃｈｅｉｉ）、プレボテラ・マルチサッカリボラックス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｓａｃｃｈａｒｉｖｏｒａｘ）、プレボテラ・ナンセイエンシス（Ｐｒｅｖｏｔｅｌｌａ ｎａｎｃｅｉｅｎｓｉｓ）、プレボテラ・オリザエ（Ｐｒｅｖｏｔｅｌｌａ ｏｒｙｚａｅ）、プレボテラ・パルディビエンス（Ｐｒｅｖｏｔｅｌｌａ ｐａｌｕｄｉｖｉｖｅｎｓ）、プレボテラ・プレウリチディス（Ｐｒｅｖｏｔｅｌｌａ ｐｌｅｕｒｉｔｉｄｉｓ）、プレボテラ・ルミニコーラ（Ｐｒｅｖｏｔｅｌｌａ ｒｕｍｉｎｉｃｏｌａ）、プレボテラ・サッカロリティカ（Ｐｒｅｖｏｔｅｌｌａ ｓａｃｃｈａｒｏｌｙｔｉｃａ ), Prevotella scopos, Prevotella shahii, Prevotella zooogleoformans, and/or Prevotella veroralis The pharmaceutical composition according to item 1. 117. The pharmaceutical composition of claim 116, wherein said Prevotella bacterium is Prevotella histicola. The Prevotella bacterium exhibits at least 95% genomic sequence identity, 16S sequence identity, and/or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). A pharmaceutical composition according to any one of claims 81 to 117, which is a strain comprising The Prevotella bacterium exhibits at least 99% genomic sequence identity, 16S sequence identity, and/or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). 119. The pharmaceutical composition of claim 118, which is a strain comprising 120. The pharmaceutical composition of claim 119, wherein said Prevotella bacterium is Prevotella strain B 50329 (NRRL Accession No. B 50329). 121. The pharmaceutical composition of any one of claims 81-120, wherein said Prevotella bacterium is a strain of Prevotella bacterium comprising one or more proteins listed in Table 1. . 122. The pharmaceutical composition of any one of claims 81-121, wherein said Prevotella bacterium is a strain of Prevotella substantially free of the proteins listed in Table 2. 123. The pharmaceutical composition of any one of claims 81-122, wherein the pharmaceutical composition comprises live, killed, or attenuated bacteria. Claims 81-122, wherein said Prevotella bacterium has been gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated, and/or oxygen-sparged. The pharmaceutical composition according to any one of . 125. The pharmaceutical composition of claim 124, wherein said Prevotella bacteria are heat inactivated at 50<0>C for 2 hours or at 90<0>C for 2 hours. 125. The pharmaceutical composition of claim 124, wherein said Prevotella bacteria are oxygen sparged at 0.1 vvm for 2 hours. 127. The pharmaceutical composition of any one of claims 81-126, wherein said Prevotella bacterium is a lyophilized Prevotella bacterium. 128. The pharmaceutical composition of Claim 127, wherein said pharmaceutical composition further comprises a pharmaceutically acceptable excipient. 129. The pharmaceutical composition of any one of claims 81-128, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species. 129. The pharmaceutical composition of any one of claims 81-128, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. 129. The pharmaceutical composition of any one of claims 81-128, wherein the Prevotella bacteria in the pharmaceutical composition are from different species. 130. The pharmaceutical composition of any one of claims 81-129, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. The pharmaceutical composition according to any one of claims 81-132, wherein said pharmaceutical composition is administered in combination with an additional therapeutic agent. 134. The pharmaceutical composition of Claim 133, wherein said additional therapeutic agent is an anti-inflammatory agent. The pharmaceutical composition according to any one of claims 81-134, wherein said pharmaceutical composition is formulated as a solid dosage form. 136. The pharmaceutical composition of Claim 135, wherein said solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof. 137. The pharmaceutical composition of claim 135 or 136, wherein said solid dosage form further comprises a pharmaceutically acceptable excipient. 138. The pharmaceutical composition according to any one of claims 135-137, wherein said solid dosage form comprises an enteric coating. The pharmaceutical composition according to any one of claims 135-138, wherein said solid dosage form is formulated for oral administration. The pharmaceutical composition according to any one of claims 81-134, wherein said pharmaceutical composition is formulated as a suspension. 141. The pharmaceutical composition of claim 140, wherein said suspension is formulated for oral administration. 142. The pharmaceutical composition according to claim 140 or 141, wherein said suspending agent comprises PBS and optionally sucrose or glucose. 141. The pharmaceutical composition of claim 140, wherein said suspension is formulated for intravenous administration. 141. The pharmaceutical composition of claim 140, wherein said suspension is formulated for intraperitoneal administration. 145. The pharmaceutical composition of claim 143 or 144, wherein said suspending agent comprises PBS. 141. The pharmaceutical composition of Claim 140, wherein said pharmaceutical composition is administered intravenously. 141. The pharmaceutical composition of claim 140, wherein said pharmaceutical composition is administered by injection, for example by subcutaneous, intradermal or intraperitoneal injection. The pharmaceutical composition according to any one of claims 140-147, wherein said suspending agent further comprises a pharmaceutically acceptable excipient. The pharmaceutical composition of any one of claims 140-148, wherein said suspending agent further comprises a buffer. 149. The pharmaceutical composition of claim 149, wherein said buffer is PBS. 151. The pharmaceutical composition of any one of claims 81-150, wherein said pharmaceutical composition further comprises one or more additional therapeutic agents. 152. The pharmaceutical composition of Claim 151, wherein said one or more additional therapeutic agents is one or more anti-inflammatory agents. The pharmaceutical composition of any one of claims 81-142 or 148-152, wherein said pharmaceutical composition is administered orally. 154. The pharmaceutical composition of any one of claims 81-153, wherein said pharmaceutical composition comprises from about 5 mg to about 900 mg total protein as determined by the Bradford assay or the BCA assay. 155. The pharmaceutical composition of any one of claims 81-154, wherein said pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by the Bradford assay or the BCA assay. 156. The pharmaceutical composition of any one of claims 81-155, wherein said pharmaceutical composition is administered to said subject with an additional therapeutic agent. 157. The pharmaceutical composition of Claim 156, wherein said additional therapeutic agent is an anti-inflammatory agent. 157. The pharmaceutical composition of Claim 156, wherein said additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukotriene receptor antagonist, an antibody, or a combination thereof. 158. The pharmaceutical composition of claim 156 or 157, wherein said pharmaceutical composition comprises said additional therapeutic agent. 157. The pharmaceutical composition of claim 156, wherein said additional therapeutic agent is an antibiotic agent. Use of a pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria for the manufacture of a medicament for the treatment or prevention of a T _H2 -mediated condition in a subject. 162. Use according to claim 161, wherein said subject is a human subject. 161. 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 said pharmaceutical composition is derived from Prevotella bacteria, claim 161 or the use according to 162. Use according to any one of claims 161 to 163, wherein said use treats said T _H 2-mediated condition. Use according to any one of claims 161 to 164, wherein said T _H2 -mediated condition is asthma, atopic dermatitis, eosinophilic disease and/or allergy. 166. Use according to claim 165, wherein the T _H2 -mediated condition is allergy, and wherein said allergy is food allergy, seasonal allergic rhinitis, and/or pet allergy. 166. Use according to claim 165, wherein said T _H2 -mediated condition is atopic dermatitis. 166. Use according to claim 165, wherein said T _H2 -mediated condition is food allergy. 169. Use according to claim 168, wherein the food allergy is peanut allergy, milk allergy, chicken egg allergy, fish allergy, shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. 169. Use according to claim 168, wherein the food allergy is peanut allergy. 169. Use according to claim 168, wherein food allergy is allergy to food antigens. 172. Use according to claim 171, wherein the food antigen is a peanut antigen, milk antigen, chicken egg antigen, fish antigen, shellfish antigen, tree nut antigen, wheat antigen, or soybean antigen. 172. Use according to claim 171, wherein said food antigen is a peanut antigen. 174. The use of any one of claims 161-173, wherein administration of said pharmaceutical composition reduces interleukin (IL)-4 levels in said subject. Use according to claim 174, wherein said IL-4 level is IL-4 protein level or IL-4 mRNA level. 176. Use according to any one of claims 161 to 175, wherein administration of said pharmaceutical composition reduces interleukin (IL)-5 levels in said subject. 177. Use according to claim 176, wherein said IL-5 level is IL-5 protein level or IL-5 mRNA level. 178. The use of any one of claims 161-177, wherein administration of said pharmaceutical composition reduces interleukin (IL)-13 levels in said subject. Use according to claim 178, wherein said IL-13 level is IL-13 protein level or IL-13 mRNA level. 179. The use of any one of claims 161-179, wherein administration of said pharmaceutical composition reduces interleukin (IL)-19 levels in said subject. 181. Use according to claim 180, wherein said IL-19 level is IL-19 protein level or IL-19 mRNA level. 182. The use of any one of claims 161-181, wherein administration of said pharmaceutical composition reduces interleukin (IL)-21 levels in said subject. 183. Use according to claim 182, wherein said IL-21 level is IL-21 protein level or IL-21 mRNA level. 184. The use of any one of claims 161-183, wherein administration of said pharmaceutical composition reduces interleukin (IL)-31 levels in said subject. Use according to claim 184, wherein said IL-31 level is IL-31 protein level or IL-31 mRNA level. 186. Use according to any one of claims 161 to 185, wherein administration of said pharmaceutical composition reduces interleukin (IL)-33 levels in said subject. 187. Use according to claim 186, wherein said IL-33 level is IL-33 protein level or IL-4 mRNA level. 188. The use of any one of claims 161-187, wherein administration of said pharmaceutical composition reduces thymic stromal lymphopoietin (TSLP) levels in said subject. 189. Use according to claim 188, wherein said TSLP level is TSLP protein level or TSLP mRNA level. 189. Use according to any one of claims 161 to 189, wherein administration of said pharmaceutical composition reduces IgGl levels in said subject. 191. Use according to claim 190, wherein said IgGl level is IgGl protein level or IgGl mRNA level. 192. The use of any one of claims 161-191, wherein administration of said pharmaceutical composition reduces IgE levels in said subject. 193. Use according to claim 192, wherein said IgE level is IgE protein level or IgE mRNA level. 194. The use of any one of claims 161-193, wherein administration of said pharmaceutical composition reduces IgA levels in said subject. 195. Use according to claim 194, wherein said IgA level is IgA protein level or IgA mRNA level. The Prevotella bacterium includes Prevotella albensis, Prevotella aminii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotellaブライアンティイ（Ｐｒｅｖｏｔｅｌｌａ ｂｒｙａｎｔｉｉ）、プレボテラ・ブッカエ（Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｅ）、プレボテラ・ブッカリス（Ｐｒｅｖｏｔｅｌｌａ ｂｕｃｃａｌｉｓ）、プレボテラ・コプリ（Ｐｒｅｖｏｔｅｌｌａ ｃｏｐｒｉ）、プレボテラ・デンタリス（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｌｉｓ）、プレボテラ・デンティコーラ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔｉｃｏｌａ）、プレボテラ・ディシエンス（Ｐｒｅｖｏｔｅｌｌａ ｄｉｓｉｅｎｓ）、プレボテラ・ヒスチコーラ（Ｐｒｅｖｏｔｅｌｌａ ｈｉｓｔｉｃｏｌａ）、プレボテラ・インターメディア（Ｐｒｅｖｏｔｅｌｌａ ｉｎｔｅｒｍｅｄｉａ）、プレボテラ・マクローサ（Ｐｒｅｖｏｔｅｌｌａ ｍａｃｕｌｏｓａ）、プレボテラ・マルシイ（Ｐｒｅｖｏｔｅｌｌａ ｍａｒｓｈｉｉ）、プレボテラ・メラニノジェニカ（Ｐｒｅｖｏｔｅｌｌａ ｍｅｌａｎｉｎｏｇｅｎｉｃａ）、プレボテラ・マイカンス（ Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella aurorolum, Prevotella aurorolum ( Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni ｊｅｊｕｎｉ）、プレボテラ・オーランティアカ（Ｐｒｅｖｏｔｅｌｌａ ａｕｒａｎｔｉａｃａ）、プレボテラ・バーロニアエ（Ｐｒｅｖｏｔｅｌｌａ ｂａｒｏｎｉａｅ）、プレボテラ・コロランス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｌｏｒａｎｓ）、プレボテラ・コルポリス（Ｐｒｅｖｏｔｅｌｌａ ｃｏｒｐｏｒｉｓ）、プレボテラ・デンタシニ（Ｐｒｅｖｏｔｅｌｌａ ｄｅｎｔａｓｉｎｉ）、プレボテラ・エノエカ（Ｐｒｅｖｏｔｅｌｌａ ｅｎｏｅｃａ）、プレボテラ・ファルセニイ（Ｐｒｅｖｏｔｅｌｌａ ｆａｌｓｅｎｉｉ）、プレボテラ・フスカ（Ｐｒｅｖｏｔｅｌｌａ ｆｕｓｃａ）、プレボテラ・ヘパリノリティカ（Ｐｒｅｖｏｔｅｌｌａ ｈｅｐａｒｉｎｏｌｙｔｉｃａ）、プレボテラ・ロエッシェイイ（Ｐｒｅｖｏｔｅｌｌａ ｌｏｅｓｃｈｅｉｉ）、プレボテラ・マルチサッカリボラックス（Ｐｒｅｖｏｔｅｌｌａ ｍｕｌｔｉｓａｃｃｈａｒｉｖｏｒａｘ）、プレボテラ・ナンセイエンシス（Ｐｒｅｖｏｔｅｌｌａ ｎａｎｃｅｉｅｎｓｉｓ）、プレボテラ・オリザエ（Ｐｒｅｖｏｔｅｌｌａ ｏｒｙｚａｅ）、プレボテラ・パルディビエンス（Ｐｒｅｖｏｔｅｌｌａ ｐａｌｕｄｉｖｉｖｅｎｓ）、プレボテラ・プレウリチディス（Ｐｒｅｖｏｔｅｌｌａ ｐｌｅｕｒｉｔｉｄｉｓ）、プレボテラ・ルミニコーラ（Ｐｒｅｖｏｔｅｌｌａ ｒｕｍｉｎｉｃｏｌａ）、プレボテラ・サッカロリティカ（Ｐｒｅｖｏｔｅｌｌａ ｓａｃｃｈａｒｏｌｙｔｉｃａ ), Prevotella scopos, Prevotella shahii, Prevotella zooogleoformans, and/or Prevotella veroralis. Use as set forth in paragraph 1. 197. Use according to claim 196, wherein said Prevotella bacterium is Prevotella histicola. The Prevotella bacterium exhibits at least 95% genomic sequence identity, 16S sequence identity, and/or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). Use according to any one of claims 161 to 197, which is a strain comprising The Prevotella bacterium exhibits at least 99% genomic sequence identity, 16S sequence identity, and/or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). 199. Use according to claim 198, which is a strain comprising. 200. Use according to claim 199, wherein the Prevotella bacterium is Prevotella strain B 50329 (NRRL Accession No. B 50329). 201. Use according to any one of claims 161 to 200, wherein said Prevotella bacterium is a strain of Prevotella bacterium comprising one or more proteins listed in Table 1. 202. Use according to any one of claims 161 to 201, wherein said Prevotella bacterium is a strain of Prevotella substantially free of the proteins listed in Table 2. Use according to any one of claims 161 to 202, wherein the pharmaceutical composition comprises live, killed or attenuated bacteria. Claims 161-202, wherein said Prevotella bacterium has been gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated, and/or oxygen-sparged. Use according to any one of 205. Use according to claim 204, wherein the Prevotella bacteria have been heat inactivated at 50<0>C for 2 hours or at 90<0>C for 2 hours. 205. The use of claim 204, wherein said Prevotella bacteria are oxygen sparged at 0.1 vvm for 2 hours. 207. Use according to any one of claims 161 to 206, wherein said Prevotella bacteria are freeze-dried Prevotella bacteria. 208. Use according to claim 207, wherein said composition further comprises a pharmaceutically acceptable excipient. Use according to any one of claims 161 to 208, wherein said Prevotella bacteria in said pharmaceutical composition are from the same species. Use according to any one of claims 161 to 208, wherein said Prevotella bacteria in said pharmaceutical composition are from the same strain. Use according to any one of claims 161 to 208, wherein said Prevotella bacteria in said pharmaceutical composition are from different species. Use according to any one of claims 161 to 209, wherein said Prevotella bacteria in said pharmaceutical composition are from the same strain. Use according to any one of claims 161 to 212, wherein said pharmaceutical composition is administered in combination with an additional therapeutic agent. 214. Use according to claim 213, wherein said additional therapeutic agent is an anti-inflammatory agent. Use according to any one of claims 161 to 214, wherein said pharmaceutical composition is formulated as a solid dosage form. 216. Use according to claim 215, wherein the solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof. 217. Use according to claim 215 or 216, wherein said solid dosage form further comprises a pharmaceutically acceptable excipient. Use according to any one of claims 215 to 217, wherein said solid dosage form comprises an enteric coating. Use according to any one of claims 215 to 218, wherein said solid dosage form is formulated for oral administration. Use according to any one of claims 161 to 214, wherein said pharmaceutical composition is formulated as a suspension. 221. Use according to claim 220, wherein the suspension is formulated for oral administration. 222. Use according to claim 220 or 221, wherein the suspending agent comprises PBS and optionally sucrose or glucose. 221. Use according to claim 220, wherein the suspension is formulated for intravenous administration. 221. Use according to claim 220, wherein the suspension is formulated for intraperitoneal administration. 225. Use according to claim 223 or 224, wherein the suspending agent comprises PBS. 221. Use according to claim 220, wherein said pharmaceutical composition is administered intravenously. 221. Use according to claim 220, wherein the pharmaceutical composition is administered by injection, for example by subcutaneous, intradermal or intraperitoneal injection. Use according to any one of claims 220-227, wherein said suspension further comprises a pharmaceutically acceptable excipient. Use according to any one of claims 220-228, wherein said suspending agent further comprises a buffer. 230. Use according to claim 229, wherein said buffer is PBS. Use according to any one of claims 161 to 230, wherein said pharmaceutical composition further comprises one or more additional therapeutic agents. 232. Use according to claim 231, wherein said one or more additional therapeutic agents is one or more anti-inflammatory agents. Use according to any one of claims 161-222 or 228-232, wherein said pharmaceutical composition is administered orally. Use according to any one of claims 161-233, wherein the pharmaceutical composition comprises from about 5 mg to about 900 mg total protein as determined by the Bradford assay or the BCA assay. 235. Use according to any one of claims 161-234, wherein the pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by the Bradford assay or the BCA assay.

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