WO2022061119A1 - Compositions et méthodes pour moduler des réponses immunitaires avec prevotella histicola - Google Patents

Compositions et méthodes pour moduler des réponses immunitaires avec prevotella histicola Download PDF

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Publication number
WO2022061119A1
WO2022061119A1 PCT/US2021/050881 US2021050881W WO2022061119A1 WO 2022061119 A1 WO2022061119 A1 WO 2022061119A1 US 2021050881 W US2021050881 W US 2021050881W WO 2022061119 A1 WO2022061119 A1 WO 2022061119A1
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solid dosage
dosage form
subject
prevotella
dose
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PCT/US2021/050881
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English (en)
Inventor
Shannon ARGUETA
Kristie BARTH
Andrea Itano
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Evelo Biosciences, Inc.
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Publication of WO2022061119A1 publication Critical patent/WO2022061119A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • Prevotella histicola is a gram-negative, non-sporulating, obligate anaerobe. It is a natural human commensal organism, and enrichment of the genus Prevotella has been associated with high-fiber, plant-based, non-Westem diets. Lower relative abundance of Prevotella in the gut microbiome is associated with obesity and in some diseases such as multiple sclerosis, whereas higher abundance is associated with an exercise-rich lifestyle and maintenance of healthy weight.
  • a human subject comprising administering (e.g., orally administering) to the subject a dose (e.g., a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of a Prevotella histicola.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the TLR2 is activated in intestinal epithelial cells (IEC) in the subject. In some embodiments, the TLR2 is activated in immune cells in the lamina intestinal of the subject. In some embodiments, the activation of TLR2 results in increased expression of IL-10 by the subject.
  • IEC intestinal epithelial cells
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a strain of a Prevotella histicola for the preparation of a medicament for the activation of TLR2 in a subject (e.g., a human subject)
  • a solid dosage form comprising bacteria of a Prevotella histicola strain for use in the activation of TLR2 in a subject (e.g., a human subject).
  • a solid dosage form comprising bacteria of a Prevotella histicola strain for the preparation of a medicament for the activation of TL.R2 in a subject (e.g., a human subject),
  • kits for enhancing IL-10 production in a human subject comprising administering (e.g. , orally administering) to the human subject a dose (e.g., a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola (e.g., a strain, composition and/or solid dose form described herein).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a strain of Prevotella histicola e.g., a strain, composition and/or solid dose form described herein.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a strain of a Prevotella histicola for use in enhancing IL-10 production in a subject (e.g., a human subject).
  • a dose e.g. , a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of & Prevotella histicola strain for use in enhancing IL-10 production in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for the preparation of a medicament for enhancing IL-10 production in a subject (e.g,, a human subject).
  • the IL-10 production is enhanced in intestinal epithelial cells (IEC) in the subject. In some embodiments, the IL-10 production is enhanced in immune cells in the lamina intestinal of the subject. In some embodiments, the IL-10 production is enhanced in mesenteric lymph nodes (MLNs) in the subject. In some embodiments, the Prevotella histicola strain increases TLR2 signaling in the subject.
  • a method of acti vating TLRl/2 and/or TLR2/6 heterodimers in a human subject comprising administering (e.g., orally administering) to the subject a dose (e.g., a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) of a Prevotella histicola strain and/or a composition (e.g. , a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a dose e.g., a therapeutically effective dose
  • a composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for use in activating TLR1/2 and/or TLR2/6 heterodimers in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for the preparation of a medicament tor activating TLR1/2 and/or TLR2/6 heterodimers in a subject (e.g., a human subject).
  • the Prevotella histicola strain activates TLR 1/2 and/or TLR2/6 heterodimers, e.g., in an in vitro assay, e.g., as described herein.
  • a me thod of instructing T cells to be less inflammatory in a subject comprising administering (e.g., orally administering) to the subject a dose (e.g. , a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for use in instructing T cells to be less inflammatory in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of & Prevotella histicola strain for the preparation of a medicament for instructing T cells to be less inflammatory in a subject (e.g., a human subject).
  • the T cells are instructed in mesenteric lymph nodes.
  • the Prevotella histicola strain (a dose (e.g., a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form)) is orally administered (e.g., and travels to the small intestine), dendritic cells interact with the Prevotella histicola strain in the small intestine, the dendritic cells travel to the mesenteric lymph nodes, and T cells trafficking through the mesenteric lymph node encounter the dendritic cells.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a method of affecting T cells that traffic to mesenteric lymph nodes in a subject comprising administering (e.g, orally administering) to the subject a dose (e.g., a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a dose e.g., a therapeutically effective dose
  • a composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for use in affecting T cells that traffic to mesenteric lymph nodes in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of & Prevotella histicola strain for the preparation of a medicament for affecting T cells that traffic to mesenteric lymph nodes in a subject (e.g., a human subject).
  • the T cells are affected in mesenteric lymph nodes.
  • a method of affecting B cells to mediate an effect on inflammation in a subject comprising administering (e.g., orally administering) to the subject a dose (e.g., a therapeutically effective dose) of a
  • Prevotella histicola strain and/or a composition comprising a strain of Prevotella histicola.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for use in affecting B cells to mediate an effect on inflammation in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for the preparation of a medi cament for affecting B cells to mediate an effect on inflammation in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a strain of a Prevotella histicola for the preparation of a medicament for the activation of (e.g., signaling through) IL-10 receptor (1L10R) in a subject (e.g., a human subject).
  • a solid dosage form comprising bacteria of a Prevotella histicola strain for use in the activation of (e.g., signaling through) IL 10 receptor (IL 10R) in a subject (e.g., a human subject),
  • IL 10R IL 10 receptor
  • a solid dosage form comprising bacteria of a Prevotella histicola strain for the preparation of a medicament for the activation of (e.g., signaling through) IL10 receptor (IL10R) in a subject (e.g., a human subject).
  • IL10R IL10 receptor
  • a method of generating inflammationresolving CD4+ T cells in a subject comprising administering (e.g., orally administering) to the subject a dose (e.g., a therapeutically effective dose) of a Prevotella histicola strain and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for use in generating inflammation -resolving CD4+ T cells in a subject (e.g., a human subject).
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • bacteria of a Prevotella histicola strain for the preparation of a medicament for generating inflammation-resolving CD4+ T cells in a subject (e.g., a human subject).
  • the Prevotella histicola strain is a strain comprising at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella histicola Strain B (NRRL accession number B 50329).
  • the Prevotella histicola strain is the Prevotella histicola Strain B (NRRL accession number B 50329).
  • the Prevotella histicola strain is a strain comprising at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at. least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella histicola Strain C (ATCC Deposit Number PTA-126140).
  • the Prevotella hislicola strain is the Prevolella histicola Strain C (ATCC Deposit Number PTA- 126140).
  • the subject e.g., human subject
  • the immunoinflammatory disorder is arthrosclerosis, arthritis (e.g., psoriatic arthritis), phlebitis, vasculitis, and lymphangitis, cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease, ileitis, proctitis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, microscopic colitis, lymphocytic-pl asm ocy tic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis, eosinophilic enterocolitis, indeterminate colitis, pseudomembranous colitis (necrotizing colitis), ischemic inflammatory bowel disease, Behcet’s disease, sarcoidosis, scleroderma, IBD-associated dysplasi
  • the dose is in the form of one or more enteric-coated capsules, optionally comprising an enteric -coating (e.g., enteric-coated capsules).
  • the dose is in the form of one or more tablets, optionally comprising an enteric-coating (e.g., enteric-coated tablets).
  • the dose is in the form of one or more mini-tablets.
  • the mini-tablets are enteric-coated minitablets.
  • the dose is in the form of a non-enteric coated capsule comprising an enteric-coated mini-tablet.
  • the subject is orally administered a plurality of doses of the Prevotella histicola strain.
  • a dose e.g., a therapeutically effective dose
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the composition (e.g., pharmaceutical composition) (e.g., solid dosage form) comprises a blend of freeze-dried powder of Prevotella histicola and excipients.
  • the pharmaceutical composition is formulated as multiple enteric-coated mini -tablets of Prevotella histicola drag product filled into HPMC capsules (MICs).
  • the pharmaceutical composition (e.g., solid dosage form) comprises excipients (e.g., pharmaceutically acceptable excipients).
  • the pharmaceutical composition comprises mannitol, colloidal silicon dioxide, hydroxypropyl cellulose, crospovidone, and magnesium stearate.
  • the solid dosage form comprises live bacteria. In some embodiments, the solid dosage form comprises nori-live bacteria. In some embodiments, the solid dosage form comprises irradiated (e.g., gamma irradiated) bacteria. In some embodiments, the solid dosage form comprises a pharmaceutically acceptable excipient. In some embodiments, the solid dosage form is formulated for oral administration. [44] In certain embodiments, provided herein are solid dosage forms comprising the Prevotella histicola strain. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is an enteric coated capsule. In some embodiments, the solid dosage form comprises a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 17mm in diameter.
  • the solid dosage form comprises a mini-tablet.
  • the mini-tablet is enteric coated.
  • the mini-tablet is from 1mm to 4mm in diameter.
  • the mini-tablet e.g., enteric coated minitablet
  • the solid dosage fonn comprises mini-tablets that comprise about 8 x 10 11 total cells of the Prevotella histicola strain (e.g., total dose of a plurality of mini -tablets).
  • the m ini-tablets e.g., enteric coated mini-tablets
  • the m ini-tablets are contained in a capsule.
  • the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule.
  • the capsule comprises a non-enteric coating (e.g., HPMC (hydroxyl propyl methyl cellulose) or gelatin) (e.g, is coated with a non-enteric coating).
  • the capsule comprises hydroxyl propyl methyl cellulose (HPMC).
  • the capsule comprises gelatin.
  • the Prevotella histicola strain (or composition or solid dose form thereof) is orally administered (e.g., and travels to the small intestine), dendritic cells interact with the Prevotella histicola strain in the small intestine, the dendritic cells travel to the mesenteric lymph nodes, and T cells trafficking through the mesenteric lymph node are affected by encountering the dendritic cells.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • the dose comprises one strain of bacteria, wherein the one strain of bacteria is a strain compri sing at least 99.9% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329).
  • the dose e.g., a therapeutically effective dose
  • the composition e.g, a pharmaceutical composition and/or a solid dosage form
  • the dose compri ses one strain of bacteri a, wherein the one strain of bacteria is the Prevotella histicola Strain B 50329 (NRRL accession number B 50329).
  • the compositions are prepared as solid dosage forms.
  • provided herein are solid dosage forms comprising the Prevotella histicola bacteria.
  • the solid dosage form comprises an enteric coating.
  • the solid dosage form is a tablet, e.g., an enteric coated tablet.
  • each tablet comprises about 3.2 x 10 11 total cells of the Prevotella histicola bacteria.
  • the solid dosage form is a capsule e.g., an enteric coated capsule.
  • each capsule comprises about 8 x 10 10 total cells of the Prevotella histicola bacteria.
  • each capsule comprises about 1.6 x 10 11 total cells of the Prevotella histicola bacteria.
  • each capsule comprises about 3.2. x 10 11 total cells (e.g., 3.35 x 10 11 total cells) of the Prevotella histicola bacteria,
  • from 1.6 x 10 10 cells to 16 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • from 8 x 10 11 cells to 16 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • from 8 x 10 10 cells to 8 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • from 8 x 10 10 cells to 1.6 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • from 1.6 x 10 11 cells to 8 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • about 8 x 10 10 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • about 1 ,6 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • about 3.2 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.
  • about 6.4 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 8 x 10 11 cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 1 .6 x 10 11 cells of the Prevotella histicola strain are administered to the subject once daily, e.g., in a solid dosage form. In some embodiments, about 1 .6 x 10 11 cells of the Prevotella histicola strain are administered to the subject twice daily, e.g., in a solid dosage form.
  • about 1.6 x 10 11 cells of the Prevotella histicola strain are administered to the subject twice daily (e.g., for 1-7 days, 3 days, 7 days, 10 days, or 14 days), and then about 1 .6 x 10 11 cells of the Prevotella histicola strain are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment), e.g., in a solid dosage form.
  • about 9.6 x 10 11 total cells of the Prevotella histicola strain are administered to the subject daily.
  • about 12.8 x 10 11 total cells of the Prevotella histicola strain are administered to the subject daily.
  • about 16 x 10 11 total cells of the Prevotella histicola strain are administered to the subject daily.
  • about 9.6 x 10 11 to about 16 x 10 11 total cells of the Prevotella histicola strain are administered to the subject daily.
  • about 9.6 x 10 1 1 to about 12.8 x 10 11 total cells of the Prevotella histicola strain are administered to the subject daily.
  • about 12.8 x 10 11 to about 16 x 10 11 total cells of the Prevotella histicola strain are administered to the subject daily.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose (e.g. , a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 6.4 x 10 11 total cells of Prevotella histicola, e.g , of Prevotella Strain B 50329 (e.g., in a solid dosage form).
  • the dose (e.g. , a therapeutically effective dose) and/or the composition comprises about 8 x 10 11 total cells of Prevotella histicola, e.g. , of Prevotella Strain B 50329 (e.g.. in a solid dosage form).
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • Prevotella histicola e.g., of Prevotella Strain B 50329. (e.g., in a solid dosage form).
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • Prevotella histicola e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • Prevotella histicola e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered, e.g., once or twice daily comprises 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 R total cells, at least 7 x 10 10 total cells, at least 8 x 10 10 total cells, at least 9 x 10 w total cells, at least 1 x
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • comprises no more than 9 x 10 11 total cells e.g., no more than 1 x 10 10 ' total cells, no more than 2 x 10 10 total ceils, no more than 3 x 10 10 total ceils, no more than 4 x 10 10 total cells, no more than 5 x 10 10 total ceils, no more than 6 x 10 10 total ceils, no more than 7 x 10 10 total cells, no more than 8 x 10 10 total cells, no more than 9 x 10 10 total cells, no more than 1 x 10 11 total cells, no more than 2 x 10 11 total cells, no more than 3 x 10 11 total cells, no more than 4 x 10 11 total cells, no more than 5 x 10 11 total cells, no more than 6 x 10 11 total cells, no more than 7 x 10 11 total cells,
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 6 x 10 9 total cells of the Prevotella bacteria. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1.6 x 10 10 total cells of the Prevotella bacteria. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a. solid dosage form) comprises about 1 .6 x 10 11 total cells the Prevotella bacteria. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 3.2 x 10 11 total cells the Prevotella bacteria. In some embodiments, the dose (e.g. , a therapeutically effective dose) and/or the composition (e.g, a pharmaceutical composition and/or a solid dosage form) comprises about 6.4 x 10 11 total cells the Prevotella bacteria.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g, a pharmaceutical composition and/or a solid dosage form) comprises about 8 x 10 11 total cells of the Prevotella bacteria. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1 .6 x 10 10 to about 8 x 10 11 total cells of the Prevotella bacteria. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g.
  • a pharmaceutical composition and/or a solid dosage form comprises about 1 .6 x 10 10 to about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1 .6 x 10 10 to about 16 x 10 11 total cells of the Prevotella bacteria.
  • the dose (e.g., a therapeutically effective dose) and/or the composition comprises about 8 x 10 11 to about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 1.6 x 10 11 to about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 12.8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 16 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g , a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 12.8 x 10 11 to about 16 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • a solid dosage form also referred to as a solid dose form
  • solid dosage forms comprising the Prevotella bacteria.
  • the solid dosage form comprises an enteric coating (e.g., HPMC coat).
  • the solid dosage form comprises about 8 x 10 w total ceils of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises about 1.6 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises about 3.2 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms). [80] In some embodiments, the solid dosage form comprises about 6.4 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises about 8 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises about 9.6 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises about 12.8 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises about 16 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).
  • the solid dosage form comprises a capsule.
  • the capsule is an enteric coated capsule.
  • the enteric coating comprises HPMC.
  • the enteric coating comprises a polymethacrylate-based copolymer.
  • the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1: 1).
  • the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1: 1) (such as Kollicoat MAE 100P).
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule is administered, e.g., once or twice daily to a subject.
  • 2 capsules are administered, e.g., once or twice daily to a subject.
  • the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder). In some embodiments, the Prevotella bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • the capsule comprises about 8 x 10 10 total ceils of the
  • Prevotella bacteria e.g., total dose of a capsule or plurality of capsules.
  • the capsule comprises about 1 .6 x 10 11 total cells of the
  • the capsule comprises about 3.2 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).
  • the capsule comprises about 6.4 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).
  • the capsule comprises about 8 x 10 11 total cells of the
  • Prevotella bacteria e.g., total dose of a capsule or plurality of capsules.
  • the capsule comprises about 9,6 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).
  • the capsule comprises about 12.8 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality' of capsules),
  • the capsule comprises about 16 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).
  • each capsule comprises about 1.6 x 10 10 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 1.6 x 10 10 total cells
  • 2 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 5 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 10 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • each capsule comprises about 8 x 10 10 total ceils of the Prevotella bacteria.
  • 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 8 x 10 10 total cells
  • 2 capsules e.g., each comprising about 8 x 10 10 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 8 x 10 w total cells
  • 5 capsules e.g., each comprising about 8 x 10 10 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 8 x 10 10 total cells
  • 10 capsules e.g., each comprising about 8 x 10 10 total cells
  • each capsule comprises about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • 1 , 2, 3, 4, 5, 6, 7, 8, 9. or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 1.6 x 10 11 total cells
  • 2 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 3 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 4 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 5 capsules e.g., each comprising about 1.6 x 10 l l total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 1 .6 x 10 11 total cells
  • 10 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • each capsule comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 3.2 x 10 11 total cells
  • 2 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 5 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 10 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • the solid dosage form comprises a tablet.
  • the tablet is an enteric coated tablet.
  • the tablet is from 5mm to 18mm in diameter.
  • the enteric coating comprises HPMC.
  • the enteric coating comprises a polymethacrylate-based copolymer.
  • the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1: 1).
  • the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P).
  • I, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject.
  • 1 tablet is administered, e.g., once or twice daily to a subject.
  • 2 tablets are administered, e.g., once or twice daily to a subject.
  • the Prevoiella bacteria in the tablet are lyophilized. In some embodiments, the Prevoiella bacteria in the tablet are lyophilized (e.g., in a powder). In some embodiments, the Prevoiella bacteria in the tablet are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • the tablet comprises about 8 x 10 10 total cells of the Prevoiella bacteria (e.g., total dose of a tablet or plurality of tablets).
  • the tablet comprises about 1.6 x 10 11 total cells of the Prevoiella bacteria (e.g., total dose of a tablet or plurality of tablets).
  • the tablet comprises about 3.2 x 10 11 total cells of the
  • Prevoiella bacteria e.g., total dose of a tablet or plurality of tablets.
  • the tablet comprises about 6.4 x 10 11 total cells of the Prevoiella bacteria (e.g., total dose of a tablet or plurality of tablets).
  • the tablet comprises about 8 x 10 11 total cells of the Prevoiella bacteria (e.g., total dose of a tablet or plurality of tablets).
  • the tablet comprises about 9.6 x 10 11 total cells of the
  • Prevoiella bacteria e.g., total dose of a tablet or plurality of tablets.
  • the tablet comprises about 12.8 x 10 11 total cells of the Prevoiella bacteria (e.g., total dose of a tablet or plurality of tablets). [110] In some embodiments, the tablet comprises about 16 x 10 11 total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).
  • each tablet comprises about 8 x 10 10 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject.
  • 1 tablet e.g., comprising about 8 x 10 10 total cells
  • 2 tablets e.g., each comprising about 8 x 10' 10 total cells
  • 3 tablets are administered, e.g., once or twice daily to a subject.
  • 4 tablets are administered, e.g., once or twice daily to a subject.
  • 5 tablets e.g., each comprising about 8 x 10 10 total cells
  • 6 tablets e.g., each comprising about 8 x 10 10 total cells
  • 8 tablets are administered, e.g., once or twice daily to a subject.
  • 10 tablets are administered, e.g., once or twice daily to a subject.
  • each tablet comprises about 1 .6 x 10 11 total cells of the Prevotella bacteria.
  • I, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject.
  • 1 tablet e.g., comprising about 1.6 x 10 11 total cells
  • 2 tablets e.g., each comprising about 1.6 x 10 1 1 total cells
  • 3 tablets are administered, e.g., once or twice daily to a subject.
  • 4 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • 5 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • 6 tablets are administered, e.g., once or twice daily to a subject.
  • 8 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • 10 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • each tablet comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject.
  • 1 tablet e.g., comprising about 3.2 x 10 11 total cells
  • 2 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 3 tablets are administered, e.g., once or twice daily to a subject.
  • 4 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 5 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 6 tablets are administered, e.g., once or twice daily to a subject.
  • 8 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 10 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 8 tablets are administered, e.g., once or twice daily to a subject.
  • 10 tablets are administered, e.g., once or twice daily to a subject.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • Prevotella bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., mini-tablets comprised in a capsule).
  • the powder can comprise lyophilized bacteria.
  • the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • the dose e g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 8 x 10 10 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 1.6 x
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 3.2 x 10 11 total cells the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 6.4 x 10 11 total cells the Prevotella bacteria.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 1.6 x 10 10 to about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 1.6 x 10 10 to about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 1.6 x 10 10 to about 16 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 8 x 10 10 to about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 1 .6 x 10 11 to about 8 x 10 11 total cells of the Prevotella bacteria.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 9.6 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 12.8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) (e.g., dose or composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10 11 to about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g.
  • a pharmaceutical composition and/or a solid dosage form (e.g., dose or composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10 11 to about 12.8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • dose or composition of the total dose administered comprises about 12.8 x 10 11 to about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 solid dosage forms are administered, e.g., once or twice daily to a subject.
  • 1 solid dosage form e.g., tablet or capsule
  • 2 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 5 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 10 total cells.
  • 6 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total ceils.
  • solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 10 total cells.
  • 10 solid dosage forms e.g., tablets or capsides
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 1 solid dosage form e.g., tablet or capsule
  • 2 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 5 solid dosage forms e.g., tablets or capsides
  • 5 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 6 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 8 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total ceils.
  • 10 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 1 solid dosage form e.g., tablet or capsule
  • 2 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 5 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x J O 1 1 total cells.
  • 6 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 11 total cells.
  • solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 10 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 1 solid dosage form e.g., tablet or capsule
  • 1 solid dosage form is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 2 solid dosage forms e.g., tablets or capsules
  • the solid dosage form e.g., each solid dose form
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 5 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 1 1 total cells.
  • 6 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 10 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • about 3.2 x 10 11 total cells includes total cell counts within ⁇ 5% of 3.2 x 10 11 total cells e.g., 3.35 x 10 11 total cells.
  • the solid dosage form is a tablet.
  • the tablet is an enteric coated tablet.
  • the enteric coated tablet is from 5mm to 18mm in diameter.
  • the tablet comprises about 8 x 10 10 total cells of the Prevotella bacteria.
  • the tablet comprises about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • the tablet comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • the Prevotella bacteria in the tablet are lyophilized.
  • the solid dosage form is a capsule.
  • the capsule is an enteric coated capsule.
  • the enteric coated capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule.
  • the capsule is a size 0 capsule.
  • the capsule comprises about 8 x 10 10 total cells of the Prevotella bacteria.
  • the capsule comprises about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • the capsule comprises about 3.2. x 10 11 total cells of the Prevotella bacteria.
  • the Prevotella bacteria in the capsule are lyophilized.
  • the solid dosage form is a tablet, e.g., an enteric coated tablet.
  • the solid dosage form is a mini-tablet, e.g., an enteric coated mini-tablet.
  • the solid dosage form is a capsule, e.g., an enteric coated capsule.
  • the enteric coating comprises a poly methacrylate -based copolymer.
  • the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1: 1).
  • the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1: 1 ) (such as Kollicoat MAE 100P or Eudragit L30-D55).
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g. , a pharmaceutical composition and/or a solid dosage form) comprising Prevotella bacteria is prepared as a powder.
  • the powder can comprise lyophilized bacteria.
  • the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises a powder comprising Prevotella bacteria.
  • the powder comprising Prevotella bacteria (e.g., at a dose provided herein) is resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage, or a food), e.g., for use in the methods provided herein.
  • a liquid such as a solution, buffer, water or other beverage, or a food
  • the Prevotella histicola strain is administered in a dose (e.g, a therapeutically effective dose) and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) (e.g., a pharmaceutical composition provided herein).
  • a composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the pharmaceutical composition is a solid dose form provided herein.
  • the pharmaceutical composition comprises a blend of freeze-dried powder of Prevotella histicola and excipients (e.g. an encapsulated freeze-dried powder of a Prevotella histicola strain provided herein and excipients).
  • the pharmaceutical composition comprises freeze-dried (e.g., lyophilized) powder of bacteria in a capsule.
  • the capsule is enteric coated.
  • the pharmaceutical composition comprises an enteric coated hydroxylpropyl methyl cellulose (HPMC) hard capsule.
  • the pharmaceutical composition comprises a formulation of Prevotella histicola Strain B comprising freeze-dried powder of Prevotella histicola and excipients.
  • the excipients include mannitol, magnesium stearate and colloidal silicon dioxide.
  • each capsule contains about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B).
  • 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules are administered to a subject daily.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules e.g., each containing about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g. , Prevotella histicola Strain B) are administered to a subject once daily.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powtier-containing capsules are administered to a subject twice daily.
  • 2 powder-containing capsules are administered to the subject daily.
  • 1 pow’der-containing capsule is administered to the subject daily.
  • each powder-containing capsule contains about 8.0 x 10 10 cells of & Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B).
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules are administered to a subject daily.
  • 2 powder-containing enteric coated capsules e.g., each containing about 8.0 x 1O 10 ceils of a Prevotella histicola strain provided herein (e.g. , Prevotella histicola Strain B)
  • 4 powder-containing enteric coated capsules e.g., each containing about 8.0 x 10 10 cells of & Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B) are administered to the subject daily.
  • 2 powder-containing enteric coated capsules e.g., each containing about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)
  • a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B
  • 2 powder-containing enteric coated capsules e.g., each containing about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)
  • 2 powdercontaining enteric coated capsules e.g., each containing about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g. , Prevotella histicola Strain B) are administered to the subject twice daily (e.g., for 1-7 days, 3 days, 7 days, 10 days, or 14 days), and then 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment).
  • a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B
  • I powder-containing enteric coated capsule e.g., containing about 8.0 x 10 10 cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B) is administered to the subject daily.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising Prevotella bacteria is prepared as a solid dose form, such as a tablet, capsule, or a powder.
  • the powder can comprise lyophilized bacteria.
  • the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises a powder comprising Prevotella bacteria.
  • the powder comprising Prevotella bacteria (e.g., at a dose provided herein) is resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage, or a food), e.g., for use in the methods provided herein.
  • a liquid such as a solution, buffer, water or other beverage, or a food
  • the dose e.g., a therapeutically effective dose
  • the composition e.g. , a pharmaceutical composition and/or a solid dosage form
  • the administration to the subject is once daily. In some embodiments, the administration to the subject is twice daily.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose (e.g , a therapeutically effective dose) and/or the composition (e.g, a pharmaceutical composition and/or a solid dosage form) is administered once daily for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g, a pharmaceutical composition and/or a solid dosage form) is administered once daily for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) is administered once daily for at least 8 weeks. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g, a pharmaceutical composition and/or a solid dosage form) is administered once daily for at least 16 weeks.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises lyophilized Prevotella bacteria, e.g., in a powder.
  • the lyophilized Prevotella bacteria is formulated into a solid dose form, such as a tablet or capsule.
  • the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises an enteric coating or micro encapsulation.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises an enteric coating or micro encapsulation.
  • the subject is a mammal. In some embodiments, the subject is a human.
  • the subject is a non-human mammal (e.g., a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee).
  • a non-human mammal e.g., a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee.
  • Figure 1 is a plot showing the blockade of TLR2 reverses the efficacy of Prevotella histicola Strain B in a. DTH model.
  • Figure 2 is a schematic diagram showing the experimental design with HEK- blue reporter cell lines to determine specificity of various microbes for the TLR1/2 and TLR2/6 heterodimers.
  • Figure 3 is a plot showing Prevotella histicola Strain B 50329 (NRRL accession number B 50329), Prevotella histicola Strain C (ATCC Deposit Number PTA- 126140), Prevotella jejuni strain, Prevotella melaninogenica strain all have with different TLR2 activation profiles.
  • Figure 4 is a plot showing species and strain-specific differences in TLR1/2/6 activity.
  • Figure 5 is a plot showing resul ts of ex vivo restimulation of cells from the mesenteric lymph nodes with TLR2 agonist Pam3CSK4.
  • Figure 6 is a graph showing the effects of Prevotella histicola Strain B 50329 ("Prevotella ” in the graph) in a model of delayed-type hypersensitivity (DTH) in the presence or absence of TLR2 blocking antibodies (Anti-TLR2), or an isotype control (IgGl).
  • Figures 7 A and 7B are a series of two graphs showing TLR1/2 (left panel) and TLR2./6 (right panel) activation in a HEK cell reporter cell line by Prevotella histicola Strain B 50329 ("Prevotella Strain B” in the graph); Prevotella histicola Strain C ("Prevotella Strain A ” in the graph); a Prevotella jejuni strain; and a Prevotella melaninogenica strain.
  • TCC total cell count.
  • Figure 7B is a graph showing the effects of Prevotella histicola Strain B 50329 (Prevotella Strain B” in the graph); Prevotella histicola Strain C ('Prevotella Strain A ” in the graph); a. Prevotella jejuni strain; and a Prevotella melaninogenica strain in a model of delayed-type hypersensitivity (DTH).
  • Prevotella histicola Strain B 50329 Prevotella Strain B” in the graph
  • Prevotella histicola Strain C 'Prevotella Strain A ” in the graph
  • DTH delayed-type hypersensitivity
  • Figure 8 is a graph showing the effects of Prevotella histicola Strain B 5032.9 ("Prevotella”) in a model of delayed-type hypersensitivity (DTH) in the presence or absence of a4 ⁇ 7 and L-selectin blocking antibodies (anti-a4 ⁇ 7 and anti-L-selectin), or an isotype control (IgG2a).
  • Prevotella Prevotella histicola Strain B 5032.9
  • DTH delayed-type hypersensitivity
  • IgG2a isotype control
  • Figure 9 is a schematic showing the adoptive T cell transfer model used in Figure 10.
  • FIG 10 is a graph showing the effects of T cells transferred from donor mice that were treated with Prevotella histicola Strain B 50329 ('‘Prevotella ”), dexamethasone, or vehicle in recipient mice in a model of delayed-type hypersensitivity (DTH).
  • Prevotella histicola Strain B 50329
  • DTH delayed-type hypersensitivity
  • Figure 11 is a graph showing the blockade of a4 ⁇ 7 integrin to prevent lymphocyte homing to the Peyer’s patches does not affect the ability' of Prevotella histicola Strain B to resolve KLH challenge-induced inflammation in the DTH model.
  • Figure 12 is a graph showing the blockade of CD62L and a4 ⁇ 7 integrin to prevent lymphocyte homing to the Peyer’s patches and mesenteric lymph nodes inhibits the ability of Prevotella histicola Strain B to resolve KLH challenge-induced inflammation in the DTH model.
  • Figure 13 is a graph showing that B cells can mediate Prevotella histicola Strain B to resolve KLH challenge-induced inflammation in the DTH model.
  • Figure 14 is a graph showing that Prevotella histicola Strain B requires IL-
  • Figure 15 is a graph showing the ability of Prevotella histicola Strain B- modified CD4+ T cells can resolve KLH challenge-induced inflammation.
  • Figure 16 is a graph showing that blockade of either TL.R2 or IL-10R does not affect the efficacy of dexamethasone to suppress a KLH DTH response.
  • Figure 17 is a graph showing that blockade of lymphocyte gut homing or depletion of B cells does not affect the efficacy of dexamethasone to suppress a KLH DTH response.
  • Administration broadly refers to a route of administration of a composition
  • IV intravenous
  • IM intramuscular
  • IT mtratumoral
  • SC subcutaneous
  • compositions or solid dosage forms described herein can be administered in any form by any effective route, including but not limited to mtratumoral, oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), intradermal, ophthalmic, (intrajnasally, local, non-oral, such as aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, (trans)rectal, vaginal, intra-arterial, and hitrathecal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., toms- and perivaginally), intravesical, intrapulmonary, intraduodenal, intragastrical, and intrabronchial.
  • transdermal e.g., using any standard patch
  • intradermal e.g., using any standard patch
  • intradermal e.g., using any standard
  • the pharmaceutical compositions or solid dosage forms described herein are administered orally, rectally, intratumoraliy, topically, intravesically, by injection into or adjacent to a draining lymph node, intravenously, by inhalation or aerosol, or subcutaneously.
  • the pharmaceutical composition or solid dosage form described herein is administered orally.
  • a “combination” of two or more microbial strains includes the physical coexistence of the two microbial strains, either in the same material or product or in physically connected products, as well as the temporal co-admimstration or co-localization of the monoclonal microbial strains.
  • the term “decrease” or “deplete” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000 or undetectable after treatment when compared to a pre-treatment state.
  • Properties that may be decreased include number of cells of an immune cell type, number of cells of a bacterial cell type, number of cells of a stromal cell type, number of cells of an myeloid derived suppressor cell type, number of fibroblasts, level of a metabolite, and level of a cytokine or chemokine.
  • Immunoinflammatory disorder refers to any disease, disorder or disease symptom caused by an activity of the immune system, including autoimmune diseases, inflammatory diseases and allergies.
  • Immune disorders include, but are not limited to, autoimmune diseases (e.g., Lupus, Scleroderma, hemolytic anemia, vasculitis, type one diabetes, Grave’s disease, rheumatoid arthritis, multiple sclerosis, Goodpasture’s syndrome, pernicious anemia and/or myopathy), inflammatory diseases (e.g,, acne vulgaris, asthma, celiac disease, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory' disease, reperfusion injury ⁇ rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis and/or interstitial cystitis), and/or an allergies (e.g., food allergies, drug allergies and/or environmental allergies).
  • autoimmune diseases e.g., Lupus, Scleroderma, hemolytic anemia, va
  • immunoinflammatory disorders include: arthrosclerosis, arthritis (e.g., psoriatic arthritis), phlebitis, vasculitis, and lymphangitis, cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease, ileitis, proctitis, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocytic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis, eosinophilic enterocolitis, indeterminate colitis, pseudomembranous colitis (necrotizing colitis), ischemic inflammatory bowel disease, Behcet’s disease, sarcoidosis, scleroderma, IBD-associated dysplasia, dysplasia associated masses or lesions, primary sclerosing cholangitis, cervicitis, chori
  • the term ‘‘increase” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 2-fold, 4-fold, 10- fold, 100-fold, 10 ⁇ 3 fold, 10 ⁇ 4 fold, 10 ⁇ 5 fold, 10 ⁇ 6 fold, and/or 10 ⁇ 7 fold greater after treatment when compared to a pre-treatment state.
  • Properties that may be increased include immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites, and cytokines.
  • Properties that may be increased include number of cells of an immune cell type, number of cells of a bacterial cell type, number of cells of a stromal cell type, number of cells of an myeloid derived suppressor cell type, number of fibroblasts, level of a metabolite, and level of a cytokine or chernokine.
  • “Innate immune agonists” or “immuno-adjuvants” are small molecules, proteins, or other agents that specifically target innate immune receptors including Toll-Like Receptors (TLR), NOD receptors, RLRs, C-type lectin receptors, STING-cGAS Pathway components, inflamniasonie complexes.
  • TLR Toll-Like Receptors
  • NOD receptors NOD receptors
  • RLRs C-type lectin receptors
  • STING-cGAS Pathway components inflamniasonie complexes.
  • LPS is a TLR-4 agonist that is bacterially derived or synthesized and aluminum can be used as an immune stimulating adjuvant.
  • Immuno-adjuvants are a. specific class of broader adjuvant or adjuvant therapy.
  • STING agonists include, but are not limited to, 2'3'- cGAMP, 3'3'-cGAMP, c-di- AMP, c-di-GMP, 2'2'-cGAMP, and 2‘3'-cGAM(PS)2 (Rp/Sp) (Rp, Sp-isomers of the bis- phosphorothioate analog of 2'3 -cGAMP).
  • TLR agonists include, but are not limited to, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR1O and TLRI i.
  • NOD agonists include, but are not limited to, N-acetylmuramyl-L-alanyl-D- isoglutamine (muramyldipeptide (MDP)), gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), and desmuramylpeptides (DMP).
  • MDP N-acetylmuramyl-L-alanyl-D- isoglutamine
  • iE-DAP gamma-D-glutamyl-meso-diaminopimelic acid
  • DMP desmuramylpeptides
  • polynucleotide and “nucleic acid” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure, and may perform any function.
  • polynucleotides coding or non-coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RN A of any sequence, nucleic acid probes, and primers.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs.
  • modifications to the nucleotide structure may be imparted before or after assembly of the polymer.
  • a polynucleotide may be further modified, such as by conjugation with a labeling component.
  • U nucleotides are interchangeable with T nucleotides.
  • the terms “'subject” or “patient” refers to any animal.
  • a subject or a patient described as “in need thereof’ refers to one in need of a treatment for a disease.
  • Mammals i.e., mammalian animals
  • mammals include humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents).
  • the subject may be a non-human mammal including but not limited to of a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee.
  • the subject or patient may be healthy, or may be suffering from an immune disorder at any developmental stage.
  • the subject is a human subject.
  • strain refers to a member of a bacterial species with a genetic signature such that it may be differentiated from closely-related members of the same bacterial species,
  • the genetic signature may be the absence of all or part of at least one gene, the absence of all or part of at least on regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the absence (“curing”) of at least one native plasmid, the presence of at least one recombinant gene, the presence of at least one mutated gene, the presence of at least one foreign gene (a gene derived from another species), the presence at least one mutated regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or a combination thereof.
  • regulatory region e.g., a promoter, a terminator,
  • strains may be identified by PCR amplification optionally followed by DNA sequencing of the genomic region(s) of interest or of the whole genome.
  • strains may be differentiated by selection or counter-selection using an antibiotic or nutrient/metabolite, respectively.
  • the term “treating” a disease in a subject or “treating” a subject having or suspected of having a disease refers to subjecting the subject to a pharmaceutical treatment, e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening.
  • “treating” refers inter alia to delaying progression, expediting remission, inducing remission, augmenting remission, speeding recovery , increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof.
  • the Prevotella strain is a strain of Prevotella histicola. In some embodiments, the Prevotella strain is Prevotella histicola Strain B (NRRL accession number B 50329).
  • the Prevotella strain is a strain comprising at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g,, at least 99.5% sequence identity, at least 99.6% sequence identity', at least 99.7% sequence identity-’, at least 99,8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic, 16S or CRISPR nucleotide sequence) of the Prevotella histicola Strain B (NRRL accession number B 50329).
  • the Prevotella strain is Prevotella histicola Strain B (NRRL accession number B 50329).
  • the Prevotella strain is Prevotella histicola Strain C (ATCC Deposit Number PTA-126140).
  • the Prevotella strain is a strain comprising at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic, 16S or CRISPR nucleotide sequence) of the Prevotella histicola Strain C (ATCC Deposit Number PTA-126140).
  • the Prevotella strain is Prevotella histicola Strain C (ATCC Deposit Number PTA-126140).
  • NRRL is a depository affording permanence of the deposit and ready' accessibility thereto by the public if a patent is granted. All restrictions on the availability to the public of the material so deposited will be irrevocably removed upon the granting of a patent. The material will be available during the pendency of the patent application to one determined by' the Commissioner to be entitled thereto under 37 CFR 1.14 and 35 U.S.C. 122.
  • the deposited material will be maintained with all the care necessary to keep it viable and uncontaminated for a period of at least five years after the most recent request for the furnishing of a sample of the deposited plasmid, and in any case, for a period of at least thirty' (30) years after the date of deposit or for the enforceable life of the patent, whichever period is longer. Applicant acknowledges its duty to replace the deposit should the depository be unable to furnish a sample when requested due to the condition of the deposit.
  • Prevotella histicola Strains B and C can be cultured according to methods known in the art.
  • Prevotella histicola can be grown in ATCC Medium 2722, ATCC Medium 1490, or other medium using methods disclosed, for example in Caballero et al., 2017. ‘‘Cooperating Commensals Restore Colonization Resistance to Vancomycin-
  • compositions comprising Prevotella histicola bacteria provided herein.
  • the pharmaceutical composition comprises whole Prevotella histicola (e.g., live bacteria, non-live, killed bacteria, or attenuated bacteria).
  • whole Prevotella histicola e.g., live bacteria, non-live, killed bacteria, or attenuated bacteria.
  • the pharmaceutical composition comprises live Prevotella histicola bacteria.
  • the pharmaceutical composition comprises non-live
  • the pharmaceutical composition comprises irradiated (e.g., gamma irradiated) Prevotella histicola bacteria.
  • the pharmaceutical composition comprises lyophilized Prevotella histicola bacteria.
  • the pharmaceutical composition comprises a blend of freeze-dried powder of Prevotella histicola and excipients.
  • the pharmaceutical composition is formulated as capsules (e.g., enteric coated capsules) of Prevotella histicola drug product.
  • the pharmaceutical composition is formulated as tablets (e.g., enteric-coated tablets) of Prevotella histicola drug product.
  • the pharmaceutical composition is formulated as multiple mini-tablets (e.g., enteric -coated mini-tablets) of Prevote Ila histicola drug product, optionally filled into capsules (e.g., HPMC capsules) (MICs).
  • mini-tablets e.g., enteric -coated mini-tablets
  • capsules e.g., HPMC capsules
  • the pharmaceutical composition comprises excipients (e.g., pharmaceutically acceptable excipients).
  • the pharmaceutical composition comprises mannitol, colloidal silicon dioxide, and magnesium stearate.
  • the pharmaceutical composition comprises mannitol, colloidal silicon dioxide, hydroxypropyl cellulose, crospovidone, and magnesium stearate.
  • the pharmaceutical composition comprises mannitol, colloidal silicon dioxide, hydroxypropyl cellulose, crospovidone, croscarmellose sodium, and magnesium stearate.
  • the Prevotella histicola is Prevotella histicola Strain B (NRRL accession number B 50329) (“Prevotella histicola Strain B”).
  • the Prevotella histicola strain is a strain comprising at least 90%, at least 91%, at least 92%, at least 93%.
  • sequence identity e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity- 7 , at least 99.8% sequence identity 7 , at least 99.9% sequence identity
  • nucleotide sequence e.g., genomic sequence, 16S sequence, CRISPR sequence
  • the Prevotella histicola is Prevotella histicola Strain C (ATCC Deposit Number PTA- 126140; “Prevotella histicola Strain C”).
  • the Prevotella histicola strain is a strain comprising at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity 7 , at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella. histicola Strain C.
  • sequence identity e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity 7 , at least 99.9% sequence
  • the pharmaceutical composition comprises about 2x10 11 , 2.1x10 11 , 2.2x10 11 , 2.3x10 11 , 2.4x10 11 , 2.5x10 11 , 2.6x10 11 , 2.7x10 11 , 2.8x10 11 , 2.9x10 11 3x10 11 , 3.1x10 11 , 3.2x10 11 , 3.3x10 11 , 3.4x10 11 , 3.5x10 11 , 3.6x10 11 , 3.7x10 “, 3.8x10 11 , 3.9x10 11 , 4x10 11 5x10 11 , 6x10 11 , 7x10 11 , 8x10 11 , 9x10 11 , 1x10 12 , 1.5x10 11 total cells of Prevotella histicola.
  • the pharmaceutical composition comprises about 1.6x10 11 to about 8x10 11 total cells of Prevotella histicola. In some embodiments, the pharmaceutical composition comprises about 1.6x10 11 total cells of Prevotella histicola. In some embodiments, the pharmaceutical composition comprises about 4.8x10 11 total cells of Prevotella histicola. In some embodiments, the pharmaceutical composition comprises about 8x10 11 total cells of Prevotella histicola.
  • total cells are determined by total cell count (e.g., determined by Coulter counter).
  • the pharmaceutical composition comprises at least about 2x10 11 2.1x10 11 , 2.2x10 11 , 2.3x10 11 , 2.4x10 11 , 2.5x10 11 , 2.6x10 11 , 2.7x10 11 , 2.8x10 11 , 2.9x10 11 , 3x10 11 , 3.1x10 11 , 3.2x10 11 , 3.3x10 11 , 3.4x10 11 , 3.5x10 11 , 3.6x10 11 , 3.7x10 11 , 3.8x 10 11 , 3.9x10 11 , 4x10 11 5x10 11 , 6x10 11 , 7x10 11 , 8x10 11 , 9x10 11 , 1x10 11 , 1.5 x10 12 total cells of Prevotella histicola.
  • the pharmaceutical composition comprises at most about 2x10 11 , 2.1x10 11 , 2.2x10 11 , 2.3x10 11 , 2.4x10 11 , 2.5x10 11 , 2.6x10 11 , 2.7x10 11 , 2.8x10 11 , 2.9x10 11 , 3x10 11 , 3.1x10 11 , 3.2x10 11 , 3.3x10 11 , 3.4x10 11 , 3.5x10 11 , 3.6x10 11 , 3.7x10 11 , 3.8x10 11 , 3.9x10 11 , 4x10 11 5x10 11 , 6x10 11 , 7x10 11 , 8x10 11 , 9x10 11 , 1x10 11 , 1.5 x 10 12 total cells of Prevotella histicola.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 50 mg to about 3 g of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g,, a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 55mg, about 550 mg, or about 2.76 g of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g. , a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g. , a pharmaceutical composition and/or a solid dosage form) comprises about 8x 10 10 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1.6x10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 3.2x10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 6.4x10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 8x10 1 1 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g , a pharmaceutical composition and/or a solid dosage form) comprises about 9.6X10 11 total cells of Prevotella hislicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 12.8x10” total cells of Prevotella hislicola, e.g., of Prevotella Strain B 50329. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g. , a pharmaceutical composition and/or a solid dosage form) comprises about 16x10 i l total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1.6 x 10 10 to about 1 .6 x 10 11 total cells of Prevotella histicola, e.g. , of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1.6 x 10 10 to about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 8 x 10 10 to about. 8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 8 x 10 10 to about 1.6 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g,, a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 1.6 x 10 11 to about 8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 9.6 x 10 11 to about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 9.6 x 10 11 to about 12.8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329, In some embodiments, the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprises about 12.8 x 10 11 to about 16 x 10 11 total cells of Prevotella hislicola, e.g., of Prevotella Strain B 50329.
  • total cells is determined by total cell count (e.g., determined by Coulter counter).
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 8 x 10 10 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 1.6 x 10 11 total cells of Prevotella histicola, e.g. , of Prevotella Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella. Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 1.6 x 10 10 to about 8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g, a pharmaceutical composition and/or a solid dosage form
  • the dose comprises about 8 x 10 10 to about 8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the bacterial composition e.g., bacterial composition
  • composition of the total dose administered, e.g., once or twice daily comprises about 8 x 10 10 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the bacterial composition e.g., bacterial composition
  • composition of the total dose administered e.g., once or twice daily
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 5032.9,
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about
  • the bacterial composition e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10 11 to about 16 x 10 11 total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • Prevotella bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., mini-tablets comprised in a capsule).
  • the powder can comprise lyophilized bacteria.
  • the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 solid dosage forms are administered, e.g., once or twice daily to a subject.
  • 1 solid dosage form e.g., tablet or capsule
  • 1 solid dosage form is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 10 total cells.
  • 2 solid dosage forms e.g., tablets or capsules
  • the solid dosage form e.g., each solid dose form
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 5 solid dosage forms e.g., tablets or capsules
  • 5 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 10 total cells.
  • 6 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 10 total cells.
  • solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 10 total cells.
  • 10 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 10 total cells.
  • 1 solid dosage form e.g., tablet or capsule
  • 2 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 5 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 6 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 8 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 10 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x 10 10 total cells.
  • 1 solid dosage form e.g., tablet or capsule
  • 1 solid dosage form is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 11 total cells.
  • 2 solid dosage forms e.g., tablets or capsules
  • the solid dosage form e.g., each solid dose form
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 5 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 6 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1.6 x 10 11 total cells.
  • 10 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 1 .6 x 10 11 total cells.
  • I solid dosage form e.g., tablet or capsule
  • is administered e.g., is for administration
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 2 solid dosage forms e.g., tablets or capsules
  • are administered e.g., are for administration
  • the solid dosage form e.g., each solid dose form
  • 3 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 4 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 5 solid dosage forms e.g., tablets or capsules
  • 5 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 6 solid dosage forms are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • 10 solid dosage forms e.g., tablets or capsules
  • the solid dosage form comprises a dose of bacteria of about 3.2 x 10 11 total cells.
  • about 3.2 x 10 11 total cells includes total cell counts within ⁇ 5% of 3.2 x 10 11 total ceils e.g., 3.35 x 10 11 total cells.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the solid dosage form comprises an enteric coating.
  • the solid dosage form is a tablet, e.g., an enteric coated tablet.
  • each tablet comprises about 8 x 10 10 total cells of the Prevotella histicola bacteria.
  • each tablet comprises about 1.6 x10 11 total cells of the Prevotella histicola bacteria.
  • each tablet comprises about 3.2 x 10 11 total cells of the Prevotella histicola bacteria.
  • the solid dosage form is a capsule, e.g., an enteric coated capsule.
  • each capsule comprises about 8 x 10 11 total cells of the Prevotella histicola bacteria.
  • each capsule comprises about 1.6 x 10 11 total cells of the Prevotella histicola bacteria.
  • each capsule comprises about 3.2 x 10 11 total cells of the Prevotella histicola bacteria.
  • the bacterial composition e.g., pharmaceutical composition is a powder.
  • the powder can be resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage or a food), e.g., for administration to a subject.
  • a dose of Prevotella histicola bacteria of about 8 x 10 10 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 1.6 x10 11 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 3.2 x 10 11 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 6.4 x 10 11 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 8 x 10 11 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 9.6 x 10 1 1 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 12.8 x 10 11 total cells are administered (e.g., are for administration) per day.
  • a dose of Prevotella histicola bacteria of about 16 x 10 11 total cells are administered (e.g., are for administration) per day.
  • the solid dosage form is a tablet.
  • the tablet is an enteric coated tablet.
  • the enteric coated tablet is from 5mm to 18mm in diameter (size refers to size prior to application of enteric coat).
  • the tablet comprises about 8 x 10 l ° total cells of the Prevotella bacteria.
  • the tablet comprises about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • the tablet comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • the Prevotella bacteria in the tablet are lyophilized.
  • the solid dosage form is a capsule.
  • the capsule is an enteric coated capsule.
  • the enteric coated capsule is a size 00, size 0, size 1 , size 2, size 3, size 4, or size 5 capsule.
  • the capsule is a size 0 capsule.
  • the capsule comprises about 8 x 10 10 total cells of the Prevote Ila bacteria.
  • the capsule comprises about 1 .6 x 10 11 total cells of the Prevotella bacteria.
  • the capsule comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • the Prevotella bacteria in the capsule are lyophilized.
  • the capsule comprises gelatin.
  • the capsule comprises HPMC.
  • the solid dosage form is a tablet, e.g., an enteric coated tablet.
  • the solid dosage form is a capsule, e.g., an enteric coated capsule.
  • the enteric coating comprises a polymethacryl ate -based copolymer.
  • the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1: 1).
  • the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1: 1) (such as Kollicoat MAE 100P or Eudragit L30-D55).
  • each tablet comprises about 8 x 10 10 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g,, once or twice daily to a subject.
  • 1 tablet e.g., comprising about 8 x 10 10 total cells
  • 2 tablets e.g., each comprising about 8 x 10 10 total cells
  • 3 tablets are administered, e.g,, once or twice daily to a subject.
  • 4 tablets are administered, e.g., once or twice daily to a subject.
  • 5 tablets e.g., each comprising about 8 x 10 10 total ceils
  • 6 tablets e.g., each comprising about 8 x 10 ! ° total cells
  • 8 tablets e.g., each comprising about 8 x 10 10 total cells
  • 10 tablets are administered, e.g., once or twice daily to a subject.
  • each tablet comprises about 1 ,6 x 10 11 total cells of the Prevotella bacteria.
  • 1 , 2, 3, 4, 5, 6, 7, 8, 9 , or 10 tablets are administered, e.g., once or twice daily to a subject.
  • 1 tablet e.g., comprising about 1 .6 x 10 11 total cells
  • 2 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • 3 tablets are administered, e.g., once or twice daily to a subject.
  • 4 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • 5 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • 6 tablets are administered, e.g., once or twice daily to a subject.
  • 8 tablets e.g., each comprising about 1 .6 x 10 11 total cells
  • 10 tablets e.g., each comprising about 1.6 x 10 11 total cells
  • each tablet comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject.
  • 1 tablet e.g., comprising about 3.2 x 10 11 total cells
  • 2 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 3 tablets are administered, e.g., once or twice daily to a subject.
  • 4 tablets e.g., each comprising about 3.2 x 10 1 1 total cells
  • 5 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 6 tablets are administered, e.g., once or twice daily to a subject.
  • 8 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 10 tablets e.g., each comprising about 3.2 x 10 11 total cells
  • 8 tablets are administered, e.g., once or twice daily to a subject.
  • 10 tablets are administered, e.g., once or twice daily to a subject.
  • each capsule comprises about 1.6 x 10 10 'total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 1.6 x 10 10 total cells
  • 2 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 5 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 1 .6 x 10 10 total cells
  • 10 capsules e.g., each comprising about 1.6 x 10 10 total cells
  • each capsule comprises about 8 x 10 10 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 8 x 10 10 total cells
  • 2 capsules e.g., each comprising about 8 x 10 10 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 8 x 10 10 total cells
  • 5 capsules e.g., each comprising about 8 x 10 10 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 8 x 10 10 total cells
  • 10 capsules e.g., each comprising about 8 x 10 10 total cells
  • each capsule comprises about 1.6 x 10 11 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 1.6 x 10 11 total ceils
  • 2 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 5 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • 10 capsules e.g., each comprising about 1.6 x 10 11 total cells
  • each capsule comprises about 3.2 x 10 11 total cells of the Prevotella bacteria.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject.
  • 1 capsule e.g., comprising about 3.2 x 10 10 total ceils
  • 2 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 3 capsules are administered, e.g., once or twice daily to a subject.
  • 4 capsules e.g., each comprising about 3.2. x 10 11 total cells
  • 5 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 6 capsules are administered, e.g., once or twice daily to a subject.
  • 8 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • 10 capsules e.g., each comprising about 3.2 x 10 11 total cells
  • the Prevotella bacteria in the capsule are lyophilized
  • the Prevotella bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.
  • At least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Prevotella strain.
  • 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Prevotella strain.
  • at least 99% of the bacteria in the composition are of the Prevotella strain.
  • the bacteria in the composition are essentially (e.g., about 100%) of the Prevotella strain.
  • At least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Prevotella histicola strain.
  • 10%, 15%, 2.0%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Prevotella histicola strain.
  • at least 99% of the bacteria in the composition are of the Prevotella histicola strain.
  • the bacteria in the composition are essentially (e.g., about 100%) of the Prevotella histicola strain .
  • the bacteria in the composition are of the Prevotella histicola strain.
  • the pharmaceutical composition is formulated as a capsule or a tablet or a mini-tablet.
  • the pharmaceutical composition comprises an enteric coating or micro encapsulation.
  • the capsule is an enteric coated capsule.
  • the tablet is an enteric coated tablet.
  • the mini-tablet is an enteric coated mini-tablet.
  • NTA nanoparticle tracking analysis
  • DLS dynamic light scattering
  • compositions for administration subjects are combined with additional active and/or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose format.
  • the pharmaceutical compositions are combined with an adjuvant such as an immuno-adjuvant (e.g, STING agonists, TLR agonists, NOD agonists).
  • an adjuvant such as an immuno-adjuvant (e.g, STING agonists, TLR agonists, NOD agonists).
  • administration of the pharmaceutical composition to an in vivo model of inflammation decreases inflammation in the in vivo model
  • blocking TLR2 e.g., by administration of a TLR2 blocking antibody
  • the composition comprises at least one carbohydrate.
  • Carbohydrate refers to a sugar or polymer of sugars.
  • saccharide polysaccharide
  • carbohydrate oligosaccharide
  • Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule.
  • Carbohydrates generally have the molecular formula C n H 2n O n .
  • a carbohydrate may be a monosaccharide, a disaccharide, tri saccharide, oligosaccharide, or polysaccharide.
  • the most basic carbohydrate is a monosaccharide, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose.
  • Disaccharides are two joined monosaccharides. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose.
  • an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units.
  • Exemplary polysaccharides include starch, glycogen, and cellulose.
  • Carbohydrates may contain modified saccharide units such as 2 ’-deoxyribose wherein a hydroxyl group is removed, 2 ’-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N- acetylglucosamine, a nitrogen -containing form of glucose (e.g., 2’-fluororibose, deoxyribose, and hexose).
  • Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.
  • the composition comprises at least one lipid.
  • a “lipid” includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans).
  • the lipid comprises at least one faty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16: 1), margaric acid (17:0), heptadecenoic acid (17:1), stearic acid (18:0), oleic acid (18: 1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20: 1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EPA), docosanoic acid (22:0), docosenoic acid (22: 1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and t
  • the composition comprises at least one supplemental mineral or mineral source.
  • supplemental mineral or mineral source examples include, without limitation: chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium.
  • Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.
  • the composition comprises at least one supplemental vitamin
  • the at least one vitamin can be fat-soluble or water-soluble vitamins.
  • Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin.
  • Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of the vitamin, and metabolites of the vitamin .
  • the composition comprises an excipient.
  • suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.
  • the excipient comprises mannitol, colloidal silicon dioxide, hydroxypropyl cellulose, crospovidone, and/or magnesium stearate.
  • the excipient is a buffering agent.
  • suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.
  • the excipient comprises a preservative.
  • suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chloro butanol, and phenol,
  • the composition comprises a binder as an excipient.
  • suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C 12 -C 18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof.
  • composition comprises a lubricant as an excipient.
  • Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.
  • the composition comprises a dispersion enhancer as an excipient.
  • suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
  • the composition comprises a disintegrant as an excipient.
  • the disintegrant is a non-effervescent disintegrant.
  • suitable non-effervescent disintegrants include starches such as com starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth.
  • the disintegrant is an effervescent disintegrant.
  • suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.
  • the composition is a food product (e.g., a food or beverage) such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed.
  • a food product e.g., a food or beverage
  • a food or beverage such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed.
  • the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers; carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, and Chinese soups; soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products, including biscuits, cookies, and the like, candies, chewing gums, gurnmies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soy-bean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, carb
  • the composition is a food product for animals, including humans.
  • the animals, other than humans, are not particularly limited, and the composition can be used for various livestock, poultry, pets, experimental animals, and the like.
  • Specific examples of the animals include pigs, cattle, horses, sheep, goats, chickens, wild ducks, ostriches, domestic ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, and the like, but the animals are not limited thereto.
  • the pharmaceutical composition provided herein is prepared as a solid dosage form comprising a Prevotella strain and a pharmaceutically acceptable carrier.
  • the solid dosage form described herein can be, e.g., a capsule. In some embodiments, the solid dosage form described herein can be, e.g., a tablet or a mini-tablet. In some embodiments, a plurality of mini-tablets can be in (e.g., loaded into) a capsule.
  • the dose is in the form of tw o, six, or ten capsules. In some embodiments, the dose of the Prevotella histicola strain is about 8 x 10 10 total cells per capsule.
  • dose is 1.6 x 10 11 total cells of the Prevotella histicola strain and the dose is in the form of two non-enteric-coated capsules. In some embodiments, the dose is 4.8 x 10 11 total cells of the Prevotella histicola strain and the dose is in the form of six non-enteric-coated capsules. In some embodiments, the dose is 8 x 10 11 total cells of the Prevotella histicola strain and the dose is in the form of ten non-enteric-coated capsules.
  • the solid dosage form comprises a tablet (> 4mm) (e.g., 5mm-17mm).
  • the tablet is a 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 1 1mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17, mm, or 18mm tablet.
  • the size refers to the diameter of the tablet, as is known in the art. As used herein, the size of the tablet refers to the size of tlie tablet prior to application of an enteric coating.
  • the solid dosage form comprises a mini-tablet.
  • the mini-tablet can be in the size range of 1mm -4 mm range.
  • the mini-tablet can be a 1mm mini-tablet, 1 .5 mm mini-tablet, 2mm mini-tablet, 3mm mini-tablet, or 4mm mini-tablet.
  • the size refers to the diameter of the mini-tablet, as is known in the art.
  • the size of the minitablet refers to the size of the mini-tablet prior to application of an enteric coating.
  • the mini-tablets can be in a capsule.
  • the capsule can be a size 00, size 0, size I, size 2, size 3, size 4, or size 5 capsule.
  • the capsule that contains the mini -tablets can comprise a single layer coating, e.g., a non-enteric coating such as HPMC (hydroxyl propyl methyl cellulose) or gelatin.
  • HPMC hydroxyl propyl methyl cellulose
  • the mini-tablets can be inside a capsule: the number of minitablets inside a capsule will depend on the size of the capsule and the size of the mini-tablets.
  • a size 0 capsule can contain 31-35 (an average of 33) mini-tablets that are 3mm mini -tablets.
  • the solid dosage form e.g., capsule or tablet or mini-tablet
  • the solid dosage form described herein can be enteric coated.
  • provided herein is a method of delivering a pharmaceutical composition described herein to a subject.
  • the subject is a mammal.
  • the subject is a human.
  • the pharmaceutical composition is administered orally once daily. In some embodiments, the pharmaceutical composition is administered orally twice daily . [273] In some embodiments, the pharmaceutical composition is administered for 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, or 16 weeks.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • tlie composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose is administered twice daily for 2. days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12. days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 2.0 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, 39 days, 40 days, 41 days, or 42 days.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose is administered once daily for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • tlie dose e.g., a therapeutically effective dose
  • tlie composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) is administered twice daily for I, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks.
  • the dose (e.g., a therapeutically effective dose) and/or the composition (e.g., a pharmaceutical composition and/or a solid dosage form) is administered twice daily for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 weeks.
  • the dose e.g., a therapeutically effective dose
  • the composition e.g., a pharmaceutical composition and/or a solid dosage form
  • the dose is administered twice daily for at least 8 weeks.
  • the dose is administered twice daily for at least 16 weeks.
  • the pharmaceutical composition is formulated as a capsule (e.g. , containing mini-tablets) or a tablet or a mini-tablet.
  • the pharmaceutical composition comprises an enteric coating or micro encapsulation.
  • the capsule is an enteric coated capsule.
  • the tablet is an enteric coated tablet.
  • the mini-tablet is an enteric coated mini-tablet.
  • the subject is a mammal. In some embodiments, the subject is a human.
  • the pharmaceutical composition is administered in conjunction with the administration of an additional therapeutic.
  • the pharmaceutical composition comprises Prevotella hisiicola bacteria co-formulated with the additional therapeutic.
  • the pharmaceutical composition is co-administered with the additional therapeutic.
  • the additional therapeutic is administered to the subject before administration of the pharmaceutical composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 2.1, 22 or 23 hours before, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days before).
  • the additional therapeutic is administered to the subject after administration of the pharmaceutical composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes after, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22 or 23 hours after, or about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13 or 14 days after).
  • the same mode of delivery is used to deliver both the pharmaceutical composition and the additional therapeutic.
  • different modes of del iv cry are used to administer the pharmaceutical composition and the additional therapeutic.
  • the pharmaceutical composition is administered orally while the additional therapeutic is administered via injection (e.g., an intravenous, and/or intramuscular injection).
  • the pharmaceutical compositions, dosage forms, and kits described herein can be administered in conjunction with any other conventional treatment. These treatments may be applied as necessary and/or as indicated and may occur before, concurrent with or after administration of the pharmaceutical compositions, dosage forms, and kits described herein.
  • the dosage regimen can be any of a variety of methods and amounts, and can be determined by one skilled in the art according to known clinical factors. As is known in the medical arts, dosages for any one patient can depend on many factors, including the subject's species, size, body surface area, age, sex, immunocompetence, and general health, the particular microorganism to be administered, duration and route of administration, the kind and stage of the disease, and other compounds such as drugs being administered concurrently. In addition to the above factors, such levels can be affected by the infectivity of the microorganism, and the nature of the microorganism, as can be determined by one skilled in the art.
  • appropriate minimum dosage levels of microorganisms can be levels sufficient for the microorganism to survive, grow' and replicate.
  • the dose of the pharmaceutical compositions described herein may be appropriately set or adjusted in accordance with the dosage form, the route of administration, the degree or stage of a target disease, and the like.
  • the general effective dose of the agents may range between 0.01 mg/kg body weight/day and 1000 mg/kg body weight/day, between 0.1 mg/kg body weight/day and 1000 mg/kg body weight/day, 0.5 mg/kg body weight/day and 500 mg/kg body weight/day, 1 mg/kg body weight/day and 100 mg/kg body weight/day, or between 5 mg/kg body weight/day and 50 mg/kg body weight/day.
  • the effective dose may be 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, or 1000 mg/kg body weight/day or more, but the dose is not limited thereto.
  • the dose administered to a subject is sufficient to prevent disease (e.g., autoimmune disease, inflammatory disease, metabolic disease), delay its onset, or slow or stop its progression.
  • disease e.g., autoimmune disease, inflammatory disease, metabolic disease
  • dosage will depend upon a variety of factors including the strength of the particular compound employed, as well as the age, species, condition, and body weight of the subject.
  • the size of the dose will also be determined by the route, timing, and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular compound and the desired physiological effect.
  • Suitable doses and dosage regimens can be determined by conventional range- finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached.
  • An effective dosage and treatment protocol can be determined by routine and conventional means, starting e.g., with a low dose in laboratory animals and then increasing the dosage while monitoring the effects, and systematically varying the dosage regimen as well. Animal studies are commonly used to determine the maximal tolerable dose (“MTD”) of bioactive agent per kilogram weight. Those skilled in the art regularly extrapolate doses for efficacy, while avoiding toxicity, in oilier species, including humans.
  • MTD maximal tolerable dose
  • the dosages of the active agents used in accordance with the invention vary’ depending on the active agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage.
  • Separate administrations can include any number of two or more administrations, including two, three, four, five or six administrations.
  • One skilled in the art can readily determine the number of administrations to perform or the desirability of performing one or more additional administrations according to methods known in the art for monitoring therapeutic methods and other monitoring methods provided herein.
  • the methods provided herein include methods of providing to the subject one or more administrations of a pharmaceutical composition, where the number of administrations can be determined by monitoring the subject, and, based on the results of the monitoring, determining whether or not to provide one or more additional administrations. Deciding on whether or not to provide one or more additional administrations can be based on a variety of monitoring results.
  • the time period between administrations can be any of a variety of time periods.
  • the time period between administrations can be a function of any of a variety of factors, including monitoring steps, as described in relation to the number of administrations, the time period for a subject to mount an immune response and/or the time period for a subject to clear the bacteria from normal tissue.
  • the time period can be a function of the time period for a subject to mount an immune response: for example, the time period can be more than the time period for a subject to mount an immune response, such as more than about one week, more than about ten days, more than about two weeks, or more than about a month; in another example, the time period can be less than the time period for a subject to mount an immune response, such as less than about one week, less than about ten days, less than about two weeks, or less than about a month.
  • the time period can be a function of the time period for a subject to clear the bacteria from normal tissue: for example, the time period can be more than the time period for a subject to clear the bacteria from normal tissue, such as more than about a day, more than about two days, more than about three days, more than about five days, or more than about a week.
  • the delivery of an additional therapeutic in combination with the pharmaceutical composition described herein reduces the adverse effects and/or improves the efficacy of the additional therapeutic.
  • the effective dose of an additional therapeutic described herein is the amount of the therapeutic agent that is effective to achieve the desired therapeutic response for a particular patient, composi tion, and mode of administration, with the least toxicity to the patient.
  • the effective dosage level can be identified using the methods described herein and will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions administered, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used m combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.
  • an effective dose of an additional therapy w ill be the amount of the therapeutic agent which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.
  • the toxicity of an additional therapy is the level of adverse effects experienced by the subject during and following treatment.
  • Adverse events associated with additional therapy toxicity include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, alopecia, anaphylasis, anemia, anxiety, lack of appetite, arthralgias, asthenia, ataxia, azotemia, loss of balance, bone pain, bleeding, blood clots, low blood pressure, elevated blood pressure, difficulty breathing, bronchitis, bruising, low white blood cell count, low red blood cell count, low platelet count, cardiotoxicity, cystitis, hemorrhagic cystitis, arrhythmias, heart valve disease, cardiomyopathy, coronary artery disease, cataracts, central neurotoxicity , cognitive impairment, confusion, conjunctivitis, constipation, coughing, cramping, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, dyspepsia, dys
  • Powders e.g., of Prevotella histicola bacteria
  • Powders can be gamma-irradiated at 17.5 kGy radiation unit at ambient temperature.
  • Frozen biomasses e.g., of Prevotella histicola bacteria
  • Frozen biomasses can be gammairradiated at 25 kGy radiation unit in the presence of dry ice.
  • the methods provided herein include the administration to a subject of a bacterial composition (e.g., pharmaceutical composition (e.g., solid dose form)) described herein either alone or in combination with an additional therapeutic.
  • a bacterial composition e.g., pharmaceutical composition (e.g., solid dose form)
  • the additional therapeutic is an immunosuppressant, or a steroid.
  • the Prevotella histicola bacteria is administered to the subject before the therapeutic is administered (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before).
  • the Prevotella histicola bacteria is administered to the subject after the therapeutic is administered (e.g,, at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours after or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 2.4, 25, 26, 27, 28, 29 or 30 days after).
  • the Prevotella histicola bacteria and the therapeutic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other).
  • the subject is administered an antibiotic before the Prevotella histicola bacteria is administered to the subject (e.g., at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before).
  • an antibiotic e.g., at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before.
  • the subject is administered an antibiotic after the Prevotella histicola bacteria is administered to the subject (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after).
  • the Prevotella histicola bacteria and the antibiotic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other).
  • antibiotics can be selected based on their bactericidal or bacteriostatic properties.
  • Bactericidal antibiotics include mechanisms of action that disrupt the cell wall (e.g., p-lactams), the cell membrane (e.g., daptomycin), or bacterial DNA (e.g., fluoroquinolones).
  • Bacteriostatic agents inhibit bacterial replication and include sulfonamides, tetracyclines, and macrolides, and act by inhibiting protein synthesis.
  • some drugs can be bactericidal in certain organisms and bacteriostatic in others, knowing the target organism allows one skilled in the art to select an antibiotic with the appropriate properties.
  • bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics. Tirus, 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, monobactams, nitrofurans, oxazolidonones, penicillins, polypeptide antibiotics, quinolones, fluoroquinolone, sulfonamides, tetracyclines, and anti-mycobacterial compounds, and combinations thereof.
  • Aminoglycosides include, but are not limited to Amikacin, Gentamicin,
  • Kanamycin, Neomycin, Netilmicin, Tobramycin, Paromomycin, and Spectinomycin are examples of the compounds listed in the following paragraphs.
  • Aminoglycosides are effective, e.g., against Gram-negative bacteria, such as Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis, and against certain aerobic bacteria but less effective against obligate/facultative anaerobes. Aminoglycosides are believed to bind to the bacterial 30S or 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Ansamycins include, but are not limited to, Geldanamycin, Herbimycin,
  • Carbacephems include, but are not limited to, Loracarbef. Carbacephems are believed to inhibit bacterial cell wall synthesis.
  • Carbapenems include, but are not limited to, Ertapenem, Doripenem, Imipenem/Cilastatin, and Meropenem. Carbapenems are bactericidal for both Gram-positive and Gram-negative bacteria as broad-spectrum antibiotics. Carbapenems are believed to inhibit bacterial cell wall synthesis.
  • Cephalosporins include, but are not limited to, Cefadroxil, Cefazolin, Cefalotin, Cefalothin, Cefalexin, Cefaclor, Cefamandoie, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil, and Ceftobiprole.
  • Cephalosporins are effective, e.g., against Gram-negative bacteria and against Gram-positive bacteria, including Pseudomonas, certain Cephalosporins are effective against methicillin-resistant Staphylococcus aureus (MRSA). Cephalosporins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial ceil walls.
  • Glycopeptides include, but are not limited to, Teicoplanin, Vancomycin, and
  • Glycopeptides are effective, e.g., against aerobic and anaerobic Gram-positive bacteria including MRSA and Clostridium difficile. Glycopeptides are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Lincosamides include, but are not limited to, Clindamycin and Lincomycin.
  • Lincosamides are effective, e.g., against anaerobic bacteria, as well as Staphylococcus, and
  • 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, e.g., against Gram-positive bacteria. Lipopeptides are believed to bind to the bacterial membrane and cause rapid depolarization.
  • Macrolides include, but are not limited to, Azithromycin, Clarithromycin,
  • Macrolides are effective, e.g., against Streptococcus and Mycoplasma.
  • Macrolides are believed to bind to the bacterial or 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.
  • Monobactams include, but are not limited to, Aztreonam. Monobactams are effective, e.g., against Gram -negative bacteria. Monobactams are believed to inhibit bacterial ceil wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Nitrofurans include, but are not limited to, Furazolidone and Nitrofurantoin.
  • Oxazolidonones include, but are not limited to, Linezolid, Posizolid, Radezolid, and Torezolid. Oxazolidonones are believed to be protein synthesis inhibitors.
  • Penicillins include, but are not limited to, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxacillin, Dicloxacillin. Flucioxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Temocillin and Ticarcillin. Penicillins are effective, e.g., against Gram-positive bacteria, facultative anaerobes, e.g., Streptococcus, Borrelia, and Treponema, Penicillins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Penicillin combinations include, but are not limited to,
  • Amoxicillin/clavulanate Ampicillin/sulbactam, Piperacillin/tazobactam, and Ticarcillin/clavulanate.
  • Polypeptide antibiotics include, but are not limited to. Bacitracin, Colistin, and Polymyxin B and E. Polypeptide Antibiotics are effective, e.g., against Gram-negative bacteria. Certain polypeptide antibiotics are believed to inhibit isoprenyl pyrophosphate involved in synthesis of the peptidoglycan layer of bacterial cell walls, while others destabilize the bacterial outer membrane by displacing bacterial counter-ions.
  • Quinolones and Fluoroquinolone include, but are not limited to, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, and Temafloxacin.
  • Quinolone s/Fluoroquinolone are effective, e.g., against Streptococcus and Neisseria.
  • Quinolones/Fluoroquinolone are believed to inhibit the bacterial DNA gyrase or topoisomerase IV. thereby inhibiting DNA replication and transcription.
  • Sulfonamides include, but are not limited to, Mafenide, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim-Sulfamethoxazole (Co- trimoxazole), and Sulfonamidochrysoidme.
  • Sulfonamides are believed to inhibit folate synthesis by competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.
  • Tetracyclines include, but are not limited to, Demeclocycline, Doxycycline,
  • Tetracyclines are effective, e.g., against Gram-negative bacteria. Tetracyclines are believed to bind to the bacterial 30S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Anti -mycobacterial compounds include, but are not limited to, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifabutin, Rifapentine, and Streptomycin.
  • Suitable antibiotics also include arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, qumupristin/dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin/clavulanate, ampicillin/sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin Pl, clarithromycin, erythromycins, furazolidone, fusidic acid, Na fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazoles, mikamycin, mutacin B-Ny266, mutacin B-JH1 140, mutacin J-T8, nisin, nisin A, novobiocin, oleando
  • the additional therapeutic is an immunosuppressive agent, a DMARD, a pain -control drug, a steroid, a non-steroidal anti-inflammatory drug (NSAID), or a cytokine antagonist, and combinations thereof.
  • a DMARD a pain -control drug
  • a steroid a non-steroidal anti-inflammatory drug (NSAID)
  • NSAID non-steroidal anti-inflammatory drug
  • Representative agents include, but are not limited to, cyclosporin, retinoids, corticosteroids, propionic acid derivative, acetic acid derivative, enolic acid derivatives, fenamic acid derivatives, Cox-2 inhibitors, lumiracoxib, ibuprophen, cholin magnesium salicylate, fenoprofen, salsalate, difunisal, tolmetin, ketoprofen, flurbiprofen, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, nabumetone, naproxen, valdecoxib, etoricoxib, MK0966; rofecoxib, acetominophen, Celecoxib, Diclofenac, tramadol, piroxicam, meloxicam, tenoxicam, droxicam, lomoxicam, isoxicam, mefanamic acid, meclofenamic acid,
  • TNF alpha antagonists e.g., TNF alpha antagonists or TNF alpha receptor antagonists
  • ADALIMUMAB Humira®
  • ETANERCEPT Endbrel®
  • INFLIXIMAB Remicade®
  • CERTOLIZUMAB PEGOL Cimzia®; CDP870
  • GOLIMUMAB Simpom®; CNTO 148
  • ANAKINRA Kineret®
  • RITUXIMAB Rrtuxan®: MabThera®
  • ABATACEPT Orencia®
  • TOCIL1ZUMAB RoActemra /Actemra®
  • integrin antagonists TYS
  • the additional therapeutic is an oral PDE4 inhibitor (such as apremilast). In some embodiments, the additional therapeutic is apremilast, etanercept, infliximab, adalimumab, ustekinumab, or secukinumab.
  • the agent is an immunosuppressive agent.
  • immunosuppressive agents include, but are not limited to, corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives, immunosuppressive drugs, cyclosporin A, mercaptopurine, azathiopurine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, cromolyn sodium, anti -leukotrienes, anti -cholinergic drags for rhinitis, TLR antagonists, inflammasome inhibitors, anti -cholinergic decongestants, mast-cell stabilizers, monoclonal anti-lgE antibodies, vaccines (e.g., vaccines used for vaccination where the amount of an allergen is gradually increased), cytokine inhibitors, such as anti-IL-6 antiboth
  • the methods and compositions described herein relate to the treatment or prevention of a disease or disorder associated a pathological immune response, such as an autoimmune disease, an allergic reaction and/or an inflammatory disease.
  • the disease or disorder is an inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis).
  • the disease or disorder is psoriasis (e.g., mild to moderate psoriasis).
  • the disease or disorder is atopic dermatitis (e.g., mild to moderate atopic dermatitis).
  • a “subject in need thereof” includes any subject that has a disease or disorder associated with a pathological immune response (psoriasis (e.g., mild to moderate psoriasis) or atopic dermatitis (e.g, mild to moderate atopic dermatitis)), as well as any subject with an increased likelihood of acquiring a such a disease or disorder.
  • psoriasis e.g., mild to moderate psoriasis
  • atopic dermatitis e.g. mild to moderate atopic dermatitis
  • compositions described herein can be used, for example, as a bacterial composition for preventing or treating (reducing, partially or completely, the adverse effects of) an autoimmune disease, such as chronic inflammatory bowel disease, systemic lupus erythematosus, psoriasis, muckle-wells syndrome, rheumatoid arthritis, multiple sclerosis, or Hashimoto's disease; an allergic disease, such as a food allergy, pollenosis, or asthma; an infectious disease, such as an infection with Clostridium difficile; an inflammatory disease such as a TNF-mediated inflammatory disease (e.g., an inflammatory disease of the gastrointestinal tract, such as pouchitis, a cardiovascular inflammatory condition, such as atherosclerosis, or an inflammatory lung disease, such as chronic obstructive pulmonary disease); a bacterial composition for suppressing rejection in organ transplantation or other situations in which tissue rejection might occur; a supplement, food, or beverage for improving immune functions; or a reagent for suppressing the autoimmune disease
  • the methods provided herein are useful for the treatment of inflammation.
  • the inflammation of any tissue and organs of the body including musculoskeletal inflammation, vascular inflammation, neural inflammation, digestive system inflammation, ocular inflammation, inflammation of the reproductive system, and other inflammation, as discussed below.
  • Immune disorders of the musculoskeletal system include, but are not limited, to those conditions affecting skeletal joints, including joints of the hand, wrist, elbow, shoulderjaw, spine, neck, hip, knew, ankle, and foot, and conditions affecting tissues connecting muscles to bones such as tendons.
  • immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis), tendonitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (including, for example, Paget's disease, osteitis pubis, and osteitis fibrosa cystic).
  • arthritis including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis
  • tendonitis synovitis, ten
  • Ocular immune disorders refers to a immune disorder that affects any structure of the eye, including the eye lids.
  • ocular immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, keratoconjunctivitis sicca (dry' eye), scleritis, trichiasis, and uveitis.
  • Examples of nervous system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, encephalitis, Guillain-Barre syndrome, meningitis, neuromyotonia, narcolepsy, multiple sclerosis, myelitis and schizophrenia.
  • Examples of inflammation of the vasculature or lymphatic system which may be treated with the methods and compositions described herein include, but are not limited to, arthrosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis.
  • Examples of digestive system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease, ileitis, and proctitis.
  • Inflammatory bowel diseases include, for example, certain art- recognized forms of a group of related conditions.
  • Crohn's disease regional bowel disease, e.g., inactive and active forms
  • ulcerative colitis e.g., inactive and active forms
  • the inflammatory bowel disease encompasses irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocylic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis and eosinophilic enterocolitis.
  • Other less common forms of IBD include indeterminate colitis, pseudomembranous colitis (necrotizing colitis), ischemic inflammatory bowel disease, Behcet’s disease, sarcoidosis, scleroderma, IBD- associated dysplasia, dysplasia associated masses or lesions, and primary sclerosing cholangitis.
  • reproductive system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, cervicitis, chorioamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tubo-ovarian abscess, urethritis, vaginitis, vulvitis, and vulvodynia,
  • the methods and compositions described herein may be used to treat autoimmune conditions having an inflammatory component.
  • Such conditions include, but are not limited to, acute disseminated alopecia universalise, Behcet's disease, Chagas' disease, chronic fatigue syndrome, dysautonomia, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, diabetes mellitus type 1, giant cell arteritis, good pasture's syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's disease, Henoch- Schonlein purpura, Kawasaki's disease, lupus erythematosus, microscopic colitis, microscopic polyarteritis, mixed connective tissue disease, Muckle- Wells syndrome, multiple sclerosis, myasthenia gravis, opsoclonus
  • T-cell mediated hypersensitivity diseases having an inflammatory component.
  • Such conditions include, but are not limited to, contact hypersensitivity, contact dermatitis (including that due to poison ivy), uticaria, skin allergies, respiratory allergies (hay fever, allergic rhinitis, house dustmite allergy) and gluten-sensitive enteropathy (Celiac disease).
  • immune disorders which may be treated with the methods and compositions include, for example, appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, ulceris, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis, parotitis, percarditis, peritonoitis, pharyngitis, pleuritis, pneumonitis, prostatistis, pyelonephritis, and stomatisi, transplant rejection (involving organs such as kidney, liver, heart, lung, pancreas (e.g., islet cells), bone marrow, cornea, small bowel, skin allografts, skin homografts, and heart valve xengrafts, sewrum sickness, and graft v
  • Preferred treatments include treatment of transplant rejection, rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, Type 1 diabetes, asthma, inflammatory bowel disease, systemic lupus erythematosis, psoriasis, chronic obstructive pulmonary' disease, and inflammation accompanying infectious conditions (e.g., sepsis).
  • the methods and compositions described herein may be used to treat a dysbiosis.
  • TLR2 is required for Prevotella histicola Strain B efficacy in Delayed Type Hypersensitivity Model (DTH)
  • TLR4 and TLR2 are both expressed by intestinal epithelial cells (IEC), as well as by immune cells in the lamina intestinal epithelial cells (IEC), as well as by immune cells in the lamina intestinal epithelial cells (IEC), as well as by immune cells in the lamina intestinal epithelial cells (IEC), as well as by immune cells in the lamina intestinal. TLR4 recognizes bacterial endotoxin, and TLR2 is activated by a wide range of microbial molecules from Gram-positive and Gramnegative bacteria including peptidoglycans, lipoproteins, and lipoteichoic acid, which makes either or both receptors possible candidates for mediating part of the cellular recognition of Prevotella hisicola strain B. In Delayed Type Hypersensitivity (DTH) studies in which the activity of either TLR4 or TLR2 was inhibited via mutation or blocking antibody, respectively, only TLR2 was required tor Prevotella hisicola strain B efficacy.
  • DTH Delayed Type
  • TLR1/2 and TLR2/6 heterodimers recognize different structural motifs on bacteria and signaling through these receptors results in different outcomes in immune cell function.
  • Prevotella hisicola strain B and that these interactions can result in sustained effects, even after Prevotella hisicola strain B has passed from the gut.
  • PRRs Pattern Recognition Receptors
  • FIG. 1 shows blockade of TLR2 reverses the efficacy of Prevotella histicola strain B.
  • TLR2 forms heterodimers with TLR1 and TLR6, to mediate different responses to bacterial lipoproteins and peptidoglycans.
  • TLRl/2 and TLR2/6 are expressed by intestinal epithelial cells as well as immune cells. Efficacy is retained in TLR4 mutant mice
  • Blockade of TLR2 also results in reduction of CD4 T cells, B cells (including the B10 regulatory’ population) and NK cells (data not shown).
  • Example 2 Prevotella strains show differential ability to activate TLRl/2 and TLR2/6 [335] The objective of the studies was to determine specificity of various microbes for the TLRl/2 and TLR2/6 heterodimers.
  • Figure 2 shows the experimental design schematic with HEK-blue reporter cell lines. Various TL.R agonist controls were tested (data not shown). TLR2/6 responded strongly to high dose PAM3CSK4. TLRl/2 does not respond to FSL- 1.
  • HEK-blue reporter cell lines expressing TLR.1/2 or TLR2/6 heterodimers exclusively reveal differences between microbes.
  • Figure 4 shows species and strain -specific differences in TLR1/2/6 activity’.
  • TLRl/2 or TLR2/6 heterodimers heterodimers shows the strongest overall TLR2 stimulatory activity.
  • Gamma irradiated Veillonella parvula Strain A (ATCC Deposit Number PTA-125691) is a strong TLR2/6 agonist, with no TLRl/2 agonism observed.
  • Prevotella histicola Strain C (ATCC Deposit Number PTA-126140) is a moderately strong TLRl /2 agonist, with no TLR2/6 agonism observed.
  • Prevotella jejuni strain and Prevotella melaninogenica strain are non-efficacious microbes in the DTH model and are both moderate to strong TLR1/2 agonists and moderate to low TLR2/6 agonists.
  • TLR2 blockade prevents Pam3CSK4-induced IL-10 induction in the gutdraining lymph nodes
  • TLR2 blockade results in less IL-10 production from mesenteric lymph node cells stimulated with TL.R2 agonist Pam3CSK4.
  • B10 B cells can induce Treg and Tri cells from naive T cells.
  • Breg cells suppress THl-cell differentiation by the provision of interleukin (IL)- 10 and via cell-cell contact.
  • IL interleukin
  • Figure 5 shows ex vivo restimulation of cells from the mesenteric lymph nodes (MLNs) with TLR2 agonist Pam3CSK4, with and without TLR2 blockade. Results show reduction in IL-10 production after TLR2 blockade. TNFa levels were not reduced after TLR2 blockade. B cells are the major cell population that responds to Pam3CSK4 stimulation.
  • Example 4 Prevotella histicola effects on inflammation involve three steps
  • T cells trafficking through the mesenteric lymph node encounter gutmigrating dendritic cells, which instruct T cells to be less inflammatory
  • T cells leave the mesenteric lymph nodes, enter the systemic circulation where they migrate to the site of inflammation and enact their anti-inflammatory' effect in this peripheral tissue
  • Step 1 is supported by studies demonstrating that:
  • Step 2 is supported by stuthe s demonstrating that blockade of L ⁇ selectin/a4 ⁇ 7 integrin inhibits mesenteric lymph node migration of T cells in vivo and thus decreases the efficacy of Prevotella histicola Strain B in a DTH model of inflammation.
  • Step 3 is supported by studies in an adoptive T cell transfer model demonstrating that transferred Prevotella histicola Strain B-treated CD4 T cells mediate efficacy in a DTH model of inflammation.
  • Figure 6 is a graph showing the effects of Prevotella histicola Strain B 50329 ⁇ Prevotella ” in the graph) in a model of delayed-type hypersensitivity (DTH) in the presence or absence of TLR2 blocking antibodies (Anti-TLR2), or an isotype control (IgGl).
  • Mice were immunized with KLH + CFA and challenged intradermally in the ear 9 days later with KLH. Mice were treated every 3 days on the day of immunization through ear challenge with isotype (IgGl, 200 ug/dose, ip) or TLR2 blocking antibodies (200 ug/dose, ip).
  • mice were dosed daily from day 5 through the day of the ear challenge (day 8) with vehicle (PBS) or EDP 1815 (10 mg PO QD). Ear inflammation was measured on day 9. xxxxp ⁇ 0.001 by 1- way ANOVA followed by Dunnett’s test for multiple comparisons. These results demonstrate that Prevotella histicola Strain B 5032.9 requires TLR2 for reduction of ear inflammation in a model of delayed-type hypersensitivity (DTH).
  • DTH delayed-type hypersensitivity
  • Figure 7A is a series of two graphs showing TLR1/2 (left panel) and TLR2/6 (right panel) heterodimer activation in a HEK reporter cell line by Prevotella histicola Strain B 50329 (“Prevotella Strain B” in the graph); Prevotella histicola Strain C (“Prevotella Strain A ” in the graph); a Prevotella jejuni strain; and a Prevotella melaninogenica strain.
  • Figure 7B is a graph showing the effects of Prevotella histicola Strain B 50329 (“Prevotella Strain B” in the graph); Prevotella histicola Strain C (“Prevotella Strain A ” in the graph); a Prevotella jejuni strain; and a Prevotella melaninogenica strain in a model of delayed-type hypersensitivity (DTH).
  • Prevotella histicola Strain B in the graph
  • Prevotella histicola Strain C (“Prevotella Strain A ” in the graph)
  • a Prevotella jejuni strain a Prevotella melaninogenica strain in a model of delayed-type hypersensitivity (DTH).
  • DTH delayed-type hypersensitivity
  • mice were subjected to the DTH protocol as in Figure 6, dosed daily with vehicle or microbes (10 9 TCC/ dose, PO QD), and ear inflammation was measured on day 9.
  • FIG. 8 is a graph showing the effects of Prevotella histicola Strain B 50329 (“Prevotella”) in a model of delayed-type hypersensitivity (DTH) in the presence or absence of a4 ⁇ 7 and L-selectin blocking antibodies (anti-ct4p7 and anti-L-selectin), or an isotype control (IgG2a). Mice were immunized with KLH + CFA and challenged intradermally in the ear 14 days later with KLH.
  • DTH delayed-type hypersensitivity
  • IgG2a isotype control
  • mice were treated with four antibody treatments, every 2 days starting on the day of immunization through day 6 with isotype (IgG2a, 500 ug/dose, ip) or a4 ⁇ 7 and L-selectin blocking antibothe s (250 ug/dose each, ip). Mice were dosed daily from day 5 through day 8 with vehicle or Prevotella histicola Strain B 5032.9 (10 mg PO QD). Mice were rested from day 9 through day 14. Ear inflammation was measured on day 15.
  • isotype IgG2a, 500 ug/dose, ip
  • a4 ⁇ 7 and L-selectin blocking antibothe s 250 ug/dose each, ip.
  • Mice were dosed daily from day 5 through day 8 with vehicle or Prevotella histicola Strain B 5032.9 (10 mg PO QD). Mice were rested from day 9 through day 14. Ear inflammation was measured on day 15.
  • Figure 9 is a schematic showing the adoptive T cell transfer model used in
  • FIG. 10 Mice were sensitized with antigen (OVA or KLH + CFA) on day zero and then dosed daily with vehicle, dexamethasone ( 1 mg/kg, ip), or Prevotella histicola Strain B 50329 (10 mg, PO QD) on day 5 through day 9.
  • CD4 T cells were isolated from all lymph nodes and spleen and 2xl0 7 cells were adoptively transferred into untreated mice immunized four days earlier. Mice were rested for three days and then challenged intradermally in the ear on day 12 with the same antigen. Ear thickness was measured 24h later.
  • FIG. 10 is a graph showing the effects of CD4 T cells transferred from donor mice that were treated with Prevotella histicola Strain B 50329 (“Prevotella ”), dexamethasone, or vehicle in recipient mice in a model of delayed-type hypersensitivity (DTH).
  • Prevotella Prevotella histicola Strain B 50329
  • DTH delayed-type hypersensitivity
  • B cells and myeloid cells may also be directly’ affected by 7 microbe-gut interactions, and contribute to resolution of peripheral inflammation
  • Example 5 Immune modulation of human commensal bacteria in a KLH-based delayed type hypersensitivity model
  • DTH Delayed-type hypersensitivity
  • DTH can be induced in a variety of mouse and rat strains using various haptens or antigens, for example using an antigen emulsified with an adjuvant.
  • DTH is characterized by sensitization as well as an antigen-specific T cell-mediated reaction that results in erythema, edema, and cellular infiltration - especially infiltration of antigen presenting cells (APCs), eosinophils, activated CD4+ T cells, and cytokine-expressing Th2 cells.
  • APCs antigen presenting cells
  • eosinophils activated CD4+ T cells
  • cytokine-expressing Th2 cells cytokine-expressing Th2 cells.
  • the test formulations are prepared for KLH-based delayed type hypersensitivity model,
  • the DTH model provides an in vivo mechanism to study the cell- mediated immune response, and resulting inflammation, following exposure to a specific antigen to which the mice have been sensitized.
  • Several variations of the DTH model have been used and are well known in the art (Irving C. Allen (ed.). Mouse Models of Innate Immunity: Methods and Protocols, Methods in Molecular Biology . Vol. 1031, DOI
  • KLH Keyhole Limpet Hemocyanin
  • CFA Complete Freund s Adjuvant
  • Dexamethasone a corticosteroid
  • Dexamethasone is a known anti-inflammatory that ameliorates DTH reactions in mice, and serves as a positive control for suppressing inflammation in this model (Taube and Carlsten, Action of dexamethasone in the suppression of delayed-type hypersensitivity in reconstituted SCID mice. Inflamm Res. 2000. 49(10): 548-52).
  • a stock solution of 17 mg/mL of Dexamethasone is prepared on Day 0 by diluting 6.8 mg Dexamethasone in 400 ⁇ .L 96% ethanol.
  • a working solution is prepared by diluting the stock solution 100x in sterile PBS to obtain a final concentration of 0.17 mg/mL in a septum vial for intraperitoneal dosing.
  • Dexamethasone-treated mice receive 100 ⁇ L Dexamethasone i.p. (5 mL/kg of a 0.17 mg/mL solution). Frozen sucrose serves as the negative control (vehicle).
  • mice are challenged intradermally (i.d.) with 10 pg KLH in saline (in a volume of 10 ⁇ L) in the left ear. Inflammatory’ responses are measured using methods known in the art. Ear pinna thickness is measured at 24 hours following antigen challenge.
  • Prevotella strains may be studied further using varied timing and varied doses. For instance, treatment with a Prevotella bacterial composition may be initiated at some point, either around the time of priming or around the time of DTH challenge. For example, Prevotella (1x 10 9 CFU per mouse per day) may be administered at the same time as the subcutaneous injections (day 0), or administered prior to, or upon, intradermal injection. Prevotella strains (e.g., Strain B or Strain C) may be administered at varied doses and at defined intervals, and in various combinations. For example, some mice are intravenously injected with Prevotella Strain B at a range of between 1x10 4 and 5xl0 9 bacterial cells per mouse.
  • Prevotella strains e.g., Strain B or Strain C
  • mice receive a mixture of Strain A and/or Strain B and/or Strain C. While some mice receive a. Prevotella strain through i.v. injection, other mice may receive a Prevotella strain through intraperitoneal (i.p.) injection, subcutaneous (s.c.) injection, nasal route administration, oral gavage, topical administration, intradermal (i.d.) injection, or other means of administration. Some mice may receive a Prevotella strain every day (e.g. starting on day 0), while others may' receive a Prevotella strain at alternative intervals (e.g. every other day, or once every three days).
  • the bacterial cells may be live, dead, or weakened. The bacterial cells may be harvested fresh (or frozen) and administered, or they may be irradiated or heat-killed prior to administration.
  • mice may receive between 1x10 4 and 5x10 9 bacterial ceils in an administration.
  • some bacterial cells may be irradiated at higher or lower radiation doses, for example between 15 kGy or 35 kGy.
  • Bacterial cell composition administration may be varied by route of administration, dose, and schedule. This can include oral gavage, i.v. injection, i.p. injection, i.d. injection, topical administration, or nasal route administration.
  • mice may be treated with anti-inflammatory agent(s) (e.g. anti-CDl 54, blockade of members of the TNF family, or other treatment), and/or an appropriate control (e.g. vehicle or control antibody) at various timepoints and at effective doses.
  • anti-inflammatory agent(s) e.g. anti-CDl 54, blockade of members of the TNF family, or other treatment
  • an appropriate control e.g. vehicle or control antibody
  • mice are treated with antibiotics prior to treatment.
  • antibiotics for example, vancomycin (0.5g/L), ampicillin (1.Og/L), gentamicin (1 ,0g/L) and amphotericin B (0.2g/L) are added to the drinking water, and antibiotic treatment is halted at the time of treatment or a few days prior to treatment.
  • Some immunized mice are treated without receiving antibiotics.
  • Study animals may be sacrificed by exsanguination from the orbital plexus under CO 2 /O 2 anesthesia, followed by cervical dislocation on day 10.
  • serum preparation the blood samples are allowed to clot before centrifuging. The sera are transferred into clean tubes, each animal in a separate tube.
  • both ears each ear in a separate vial
  • the spleen the mesenteric lymph nodes (MLN)
  • the entire small intestine and the colon are collected in cryovials, snap frozen and stored at ⁇ -70°C.
  • Tissues may be dissociated using dissociation enzymes according to the manufacturer’s instructions.
  • Cells are stained for analysis by flow cytometry using techniques known in the art.
  • Staining antibodies can include anti-CDl 1c (dendritic cells), anti-CD8(), anti-CD86, anti-CD40, anti-MHCll, anti ⁇ CD8a, anti-CD4, and anti-CDl 03.
  • markers that may be analyzed include pan-immune cell marker CD45, T cell markers (CD3, CD4, CDS, CD25, Foxp3, T-bet, Gata3, Roryt, Granzyme B, CD69, PD-1, CTLA-4), and macrophage/myeloid markers (CD 11b, MHCII, CD206, CD40, CSF1R, PD-L1, Gr-1, F4/80).
  • serum cytokines are analyzed including, but not limited to, TNFa, IL-17, IL-13, IL-12p70, IL12p40, IL-10, IL-6, IL-5, IL-4, IL-2, IL- lb, IFNy, GM- CSF, G-CSF, M-CSF, MIG, IP 10, MIPlb, RANTES, and MCP-1.
  • Cytokine analysis may be carried out on immune cells obtained from lymph nodes or other tissue, and/or on purified CD45+ infiltrated immune cells obtained ex vivo.
  • immunohistochemistry is carried out on various tissue sections to measure T cells, macrophages, dendritic cells, and checkpoint molecule protein expression.
  • Example 6 Capsules comprising Prevotella histicola
  • the Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).
  • the capsule was banded with an HPMC-based banding solution.
  • the banded capsule was enteric coated with a poly(methacrylic acid-co-ethyl acrylate) copolymer.
  • Example 7 Capsule comprising Prevotella histicola
  • Table ii Prevotella histicola Capsule Composition a Swedish orange V cap capsules
  • the banded capsule was enteric coated w ith Eudragit L30-D55, a poly(methacrylic acid-co-ethyl acrylate) copolymer.
  • Example 8 Tablet comprising Prevotella histicola
  • Table iii Prevotella histicola Tablet Composition [370[ The tablet is prepared as a 17.4mm x 7.1 rnm tablet. The tablet is enteric coated. The tablet contains 3.2 x 10 11 TCC of Prevotella histicola Strain B (NRRL accession number B 50329). The Prevotella histicola strain referred to above has been deposited as
  • Example 9 Efficacy of Prevotella histicola strain b requires lymphocyte homing to the mesenteric lymph node, but not the peyer’s patches for efficacy
  • Lymphocyte homing to the Peyer’s patches is not required for Prevotella histicola Strain B efficacy:
  • mice were treated with either Rat IgG2a (2.5 mg/mL, Bio X Cell, Clone: 2A3) or anti-a4 ⁇ 7 integrin (2.5 mg/mL, Bio X Cell; Clone: DATK32 respectively).
  • mice were dosed for 4 days with lyophilized Prevotella histicola Strain B powder per os (PO) or dexamethasone (0.1 mg/kg or 0.4 mg/kg) IP injection.
  • baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements (Figure 11).
  • Lymphocyte homing to the mesenteric lymph node is required for Prevotella histicola Strain B efficacy:
  • mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant.
  • mice were treated with either Rat lgG2a (5 mg/mL, Bio X Cell, Clone: 2A3) or anti-CD62L/anti-a4 ⁇ 7 mtegrin (2.5 mg/mL each, Bio X Cell; Clone: Mel-4 and DATK32 respectively).
  • mice were dosed for 4 days with lyophilized Prevotella histicola Strain B powder per os (PO) or dexamethasone (0.1 mg/kg or 0.4 mg/kg) IP injection.
  • baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 2.4 hours, the change in ear thickness was evaluated and compared to baseline measurements (Figure 12).
  • mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On days 0, 3, 6, and 9, mice were treated with Rat IgG2b (2 mg/mL, Bio X Cell, Clone: RG7/11.1) or anti-CD20 (2 mg/mL, BioLegend, Clone:
  • mice were dosed for 4 days with dexamethasone (0,1 mg/kg or 0.4 mg/kg) IP injection.
  • baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements (Figure 13).
  • Example 11 IL-10 Receptor (IL-10R) signaling is required for efficacy Prevotella histicola Strain B
  • mice were treated with either Rat IgGl (2 mg/mL, Bio X Cell, Clone: TNP6A7) or anti-IL10R (2 mg/mL, Bio X Cell, Clone: 1BL3A) by intraperitoneal (IP) injection.
  • IP intraperitoneal
  • mice were dosed for 4 days with lyophilized Prevotella histicola Strain B powder per os (PO) or dexamethasone (0.1 mg/kg or 0.4 mg/kg) IP injection.
  • baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements ( Figure 14).
  • Example 12 Oral administration of Prevotella histicola Strain B generates inflammation-resolving CD4+ T cells that can be transferred to Strain B-nai've mice
  • ‘donor’ mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant.
  • ‘donor’ mice were dosed for 4 days with lyophilized Prevotella histicola Strain B powder per os (PO) or dexamethasone (0.1 mg/kg or 0.4 mg/kg) intraperitoneally (IP) and ‘recipient’ mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant.
  • PO Prevotella histicola Strain B powder per os
  • IP intraperitoneally
  • mice were euthanized and CD4+ T cells were isolated by negative selection from pooled and homogenized spleens and lymph nodes (brachial, axillary, and inguinal). Cell suspensions were resuspended in PBS and diluted to a cell density of 1x10 7 ' ceils/mL. Isolated CD4+ T cells were then transferred into ‘recipient’ mice by IP injection. On day 12, baseline ear thickness was measured using calipers, then ‘recipient’ mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements (Figure 15).
  • Example 13 The mechanism of action of dexamethasone is distinct from that of Prevotella histicola Strain B
  • Dexamethasone does not require TLR2 or IL-10R signaling for efficacy:
  • mice were treated with either Rat IgG2a (2 mg/mL, Bio X Cell, Clone: 2A3), anti-TLR2 (2 mg/mL, Invivogen; Clone: C9A12), Rat IgGl (2 mg/mL, Bio X Cell, Clone: TNP6A7), or anti-ILl OR (2 mg/mL, Bio X Cell, Clone: 1B1.3A) by intraperitoneal (IP) injection.
  • IP intraperitoneal
  • mice were dosed for 4 days with dexamethasone (0.1 mg/kg or 0,4 mg/kg) IP injection.
  • mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements (Figure 16), Dexamethasone does not require lymphocyte homing to the gut or B cells for efficacy: [381] Mice were immunized by subcutaneous injection with KLH emulsified with
  • mice in Rat IgG2a and anti- CD62L/anti-a4 ⁇ 7 integrin groups were treated with either Rat IgG2a (5 mg/mL, Bio X Ceil, Clone: 2A3) or anti-CD62L/anti-a4 ⁇ 7 integrin (2.5 mg/mL each, Bio X Cell; Clone: Mel-4 and DATK32 respectively).
  • mice in Rat IgG2b and anti-CD20 integrin groups were treated with Rat IgG2b (2 mg/rnL, Bio X Cell, Clone: RG7/11.1), or anti-CD20 (2 mg/rnL, BioLegend, Clone: SA271G2) by intraperitoneal (IP) injection.
  • mice were dosed for 4 days with dexamethasone (0.1 mg/kg or 0.4 mg/kg) IP injection.
  • baseline ear thickness was measured using calipers, then mice were challenged by intradermal ear injection with KLH. After 24 hours, the change in ear thickness was evaluated and compared to baseline measurements (Figure 17).

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Abstract

La présente invention concerne des méthodes et des compositions associées à des bactéries Prevotella utiles en tant qu'agents immunomodulateurs comprenant, par exemple, l'activation de TLR2, ce qui permet de réduire l'inflammation chez un sujet et le traitement d'un trouble immuno-inflammatoire.
PCT/US2021/050881 2020-09-21 2021-09-17 Compositions et méthodes pour moduler des réponses immunitaires avec prevotella histicola WO2022061119A1 (fr)

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