Compositions and methods for treating TH2-mediated conditions using Prevotella

Abstract

Provided herein are therapeutic agents, e.g., T, such as atopic dermatitis and / or food allergies. H Compositions and methods relating to Prevotella bacteria that may be useful as therapeutic agents for the treatment of HIV-2 mediated conditions.

Description

[Technical Field]

[0001] Related Applications This application claims priority to and the benefit of the filing dates of U.S. Provisional Application No. 62 / 864,886, filed June 21, 2019, and U.S. Provisional Application No. 62 / 910,920, filed October 4, 2019, both of which are incorporated herein by reference in their entireties. [Background technology]

[0002] Helper T(T H ) cells (CD4 + T cells) orchestrate the adaptive immune response by secreting cytokines that affect the activity of other immune cells, such as B cells, other T cells, eosinophils, basophils, mast cells, and macrophages.

[0003] Naive T H When cells are activated, various T H They differentiate into one of several cell subsets, each of which is involved in regulating one aspect of the immune response by secreting a specific set of cytokines. H T cells secrete IFN-γ and are involved in enhancing cell-mediated immune responses to viruses and intracellular bacteria. H T-2 cells secrete IL-4, IL-5, IL-9, IL-10, IL-13, and IL-25, and are involved in enhancing humoral immune responses, particularly against extracellular parasites such as helminths. H 17 cells secrete IL-17 and mediate inflammatory responses, such as responses to fungi (among other pathogens).

[0004] T H Which T subsets are activated? H The differentiation of these cells is determined in part by the presence of certain polarizing cytokines. For example, naive T H When cells are activated in the presence of IFN-γ, T H On the other hand, naive TH When cells are activated in the presence of IL-4, T H Therefore, activated T H The secretion of IFN-γ by T cells induces other T cells to H 1 subset, whereas activated T H The secretion of IL-4 by T cells induces other T cells to H This chain effect can polarize T H Cell differentiation can have a broad impact on a person's overall immune response. Indeed, many diseases and disorders are caused by T H 2 Diseases and disorders associated with immune responses include, but are not limited to, allergies (e.g., food allergies, insect-induced allergies, drug allergies, or allergic rhinitis), asthma, and atopic dermatitis. Summary of the Invention [Problem to be solved by the invention]

[0005] Therefore, such T H 2-mediated state (T H T to treat 2-mediated condition H 1. To promote immune responses and / or T H 2 Novel compositions and methods for inhibiting immune responses are needed. [Means for solving the problem]

[0006] As disclosed herein, pharmaceutical compositions comprising bacteria of the genus Prevotella have therapeutic effects and can be used to treat one or more T. H Such T H2-mediated conditions include, but are not limited to: allergic rhinitis, asthma, atopic dermatitis, urticaria, angioedema, allergies (e.g., food allergies, insect-induced allergies, drug allergies), anaphylaxis, and eosinophilia.

[0007] In some aspects, provided herein are methods for determining whether T H In certain embodiments, the method comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a bacterium of the genus Prevotella.

[0008] In certain aspects, provided herein are one or more T H

[0013] Accordingly, in certain embodiments, provided herein are pharmaceutical compositions comprising bacteria of the genus Prevotella useful for the treatment or prevention of T. 2-mediated conditions. H A pharmaceutical composition comprising a bacterium of the genus Prevotella for use in the treatment or prevention of a B. diffusa-mediated condition.

[0009] In certain aspects, provided herein are methods for treating T H 2. Use of a pharmaceutical composition comprising a bacterium of the genus Prevotella for the preparation of a medicament for the treatment or prevention of a .beta.-mediated condition.

[0010] In certain embodiments, this T H The two-mediated condition is an allergy, atopic dermatitis, asthma, urticaria, angioedema, anaphylaxis, eosinophilia, or a combination thereof.

[0011] In some embodiments, T HThe two-mediated condition is an allergy. In certain embodiments, the allergy is allergic rhinitis, a food allergy, an insect-induced allergy, or a drug allergy. In some embodiments, the allergy is a food allergy. In some embodiments, the food allergy may include an allergy to eggs, milk, peanuts, tree nuts (e.g., walnuts), fish, shellfish, wheat, soy, or a combination thereof.

[0012] In some embodiments of any one of these aspects, the subject is a human. In some embodiments, the subject is a non-human animal.

[0013] In some embodiments, at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of the total microbial content of the pharmaceutical composition is bacteria of the genus Prevotella or biological material derived from bacteria of the genus Prevotella.

[0014] In certain embodiments of any one of the aspects disclosed herein, the bacteria of the genus Prevotella comprise at least one protein having an amino acid sequence selected from SEQ ID NOs: 1-41. Additionally, or alternatively, in some embodiments, the bacteria of the genus Prevotella are substantially free of at least one or more of the proteins having an amino acid sequence selected from SEQ ID NOs: 42-69.

[0015] In some embodiments of any one of the aspects disclosed herein, the Prevotella bacteria include bacteria of the following species: Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, and Prevotella dyscens. disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivariae salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensistimonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludiviens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, Prevotella veroralis, or a combination thereof. In some embodiments, bacteria of the genus Prevotella may include bacteria of the species Prevotella histicola.

[0016] In some embodiments, a Prevotella bacterium may include a strain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% (e.g., at least 99.1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100%) genomic sequence identity, 16S ribosomal ribonucleic acid sequence identity, and / or regularly spaced short palindromic repeat sequence identity to Prevotella histicola strain B 50329 (NRRL Accession: B 50329). In some embodiments, the Prevotella bacteria include Prevotella histicola strain B 50329 (NRRL Accession: B 50329).

[0017] In some embodiments, the Prevotella bacterium is a strain of Prevotella bacteria that comprises a protein listed in Table 1 and / or a gene encoding a protein listed in Table 1. In some embodiments, the Prevotella bacterium is a strain of Prevotella bacteria that is free of or substantially free of a protein listed in Table 2 and / or a gene encoding a protein listed in Table 2. In some embodiments, the Prevotella histicola bacterium is a strain of Prevotella histicola bacteria that comprises a protein listed in Table 1 and / or a gene encoding a protein listed in Table 1. In some embodiments, the Prevotella histicola bacterium is a strain of Prevotella histicola bacteria that is free of or substantially free of a protein listed in Table 2 and / or a gene encoding a protein listed in Table 2.

[0018] In certain embodiments, the pharmaceutical composition comprises a single species of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises multiple species of Prevotella bacteria (e.g., 2, 3, 4, or 5 species). In certain embodiments, the pharmaceutical composition comprises a single strain of Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises multiple strains of Prevotella bacteria (e.g., 2, 3, 4, or 5 strains). In certain embodiments, the pharmaceutical composition comprises a single strain of Prevotella histicola bacteria. In some embodiments, the pharmaceutical composition comprises multiple strains of Prevotella histicola bacteria (e.g., 2, 3, 4, or 5 strains).

[0019] In some embodiments, the Prevotella bacteria in the pharmaceutical composition include live, killed, or attenuated bacteria. In some embodiments, the Prevotella bacteria in the pharmaceutical composition include live bacteria. In some embodiments, the pharmaceutical composition includes bacteria that have been gamma-irradiated, UV-irradiated, heat-inactivated (e.g., at 50°C for 2 hours and 90°C for 2 hours), acid-treated, or oxygen-sparged (at 0.1 vvm for 2 hours). In certain embodiments, the Prevotella bacteria in the pharmaceutical composition include lyophilized bacteria. In some embodiments, the pharmaceutical composition further includes a pharmaceutically acceptable excipient.

[0020] In some embodiments of any one of the aspects disclosed herein, administration of the pharmaceutical composition to a subject results in an increase in T lymphocyte counts in the subject (e.g., in the mesenteric lymph nodes or cervical lymph nodes). H 2 protein and / or T H By way of example, in certain embodiments, administration of the pharmaceutical composition may result in a decrease in the level of mRNA encoding T2 protein. H 2 protein and / or T H The level of mRNA encoding the T2 protein was measured using the pharmaceutical composition before administration. H 2 protein and / or T H In certain embodiments, the level of the mRNA encoding the T2 protein is lower in the subject compared to the level of the mRNA encoding the T2 protein. H The T2 protein is interleukin-4 (IL-4), interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-33, thymic stromal lymphopoietin, immunoglobulin G1, immunoglobulin E, immunoglobulin A, or a combination thereof. In certain embodiments, the T2 protein is HThe T2 protein is IL-4, IL-13, IL-5, IL-31, IL-33, or a combination thereof. H In certain embodiments, the T2 protein is IL-13, IL-5, IL-31, or a combination thereof. H In certain embodiments, the T2 protein is IL-13. H In certain embodiments, the T2 protein is IL-31. H The 2-mRA is Il4, Il5, IL31, Il33, Tslp, Ccl9, Ccr4, or a combination thereof. H The 2-mRA is Il4, Il5, Il33, Il17a, Il1b, Tslp, or a combination thereof. H The 2-mRA is Il4, Il5, Tslp, Ccr4, Il19, or a combination thereof. H 2-mRA is Il5, Il31, and Ccr4, or a combination thereof. In certain embodiments, this T H 2-mRA is Il5.

[0021] In some embodiments of one of the aspects disclosed herein, administration of the pharmaceutical composition to a subject can cause a decrease in the level of a mast cell-associated protein and / or mRNA encoding a mast cell-associated protein in the subject (e.g., in the jejunum). In certain embodiments, the mast cell mRNA is Mcpt1. By way of example, in certain embodiments, upon administration of the pharmaceutical composition, the level of the mast cell-associated protein and / or mRNA encoding a mast cell-associated protein is lowered in the subject when compared to the level of the mast cell-associated protein and / or mRNA encoding a mast cell-associated protein before administration of the pharmaceutical composition.

[0022] In some embodiments of any one of the aspects disclosed herein, administration of the pharmaceutical composition to a subject may cause an increase in the level of IL-10 in the subject (e.g., in the spleen or mesenteric lymph nodes). By way of example, in certain embodiments, upon administration of the pharmaceutical composition, the level of IL-10 and / or mRNA encoding IL-10 is increased in the subject (e.g., in the spleen or mesenteric lymph nodes) when compared to the level of IL-10 and / or mRNA encoding IL-10 before administration of the pharmaceutical composition.

[0023] In some embodiments of any one of the aspects disclosed herein, the subject is administered an additional therapeutic agent. In some embodiments, the additional therapeutic agent is an anti-inflammatory agent. In certain embodiments, the additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukotriene receptor antagonist, an antibody, or a combination thereof. For example, the additional therapeutic agent can be: acrivastine, albuterol, alimemazine, ANB020, and benralizumab, antazoline, AS1517499, AS1810722, astemizole, azathioprine, AZD1981, azelastine, beclomethasone, bepotastine, betamethasone, BI671800, bilastine, bromazine, brompheniramine, budesonide, budesonide-formoterol, carbinoxamine, cetirizine, chlorcyclizine, chloropyramine, chlorphenamine, ciclesonide, cyclosporine, cimetidine, clemastine, cortisone, crisaborole, cromolyn, cyclizine, cyproheptadine, CYT003., dapsone, desloratadine, dexamethasone, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimethindene, diphenhydramine, doxylamine, dupilumab, ebastine, ephedrine, epinephrine, famotidine, fexofenadine, flunisolide, fluticasone, fluticasone furoate, fluticasone propionate, fluticasone-salmeterol, formoterol, formoterol- Mometasone, GSK3772847, hydroxychloroquine, hydroxyzine, imiquimod, interferon gamma-1b, ipratropium, ketotifen, lebrikizumab, levalbuterol, levocabastine, levocetirizine, levomethamphetamine, loratadine, meclizine, meclofenamate sodium, mepolizumab, mepyramine, methotrexate, methylprednisolone, mizolastine, MK-886, mometasone zolpidem, montelukast, mycophenolate, mycophenolate mofetil, naphazoline, OC000459, olopatadine, omalizumab, orphenadrine, oxymetazoline, pheniramine, phenylephrine, phenylpropanolamine, pimecrolimus, prednisolone, prednisone, promethazine, propylhexedrine, pseudoephedrine, quifenadine, ranitidine, resiquimod, reslizumab, RG61 49 / AMG282, rupatadine, salmeterol, SB010, sirolimus, sulfasalazine, synephrine, tacrolimus, terfenadine, tetrizoline, theofelline, tixocortol, tralokinumab, tramazoline, triamcinolone, triamcinolone acetonide, tripelennamine, triprolidine, vitamin D, xylometazoline, YM-341619, zafirlukast, zileuton, or a combination thereof. In certain embodiments, the additional therapeutic agent may be included as part of the pharmaceutical composition or may be separate.

[0024] In some embodiments, the pharmaceutical composition is administered orally, intravenously, subcutaneously, intradermally, or intraperitoneally. In some embodiments, the pharmaceutical composition is administered orally.

[0025] In certain embodiments, the pharmaceutical composition has a total protein content of at least 5 mg (e.g., at least 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg) (e.g., as determined by a Bradford assay, as determined by a BSA assay). g, 290mg, 300mg, 310mg, 320mg, 330mg, 340mg, 350mg, 360mg, 370mg, 380mg, 390mg, 400mg, 410mg, 420mg, 430mg, 440mg, 450mg, 460mg, 470mg, 480mg, 490 mg, 500mg, 510mg, 520mg, 530mg, 540mg, 550mg, 560mg, 570mg, 580mg, 590mg, 600mg, 610mg, 620mg, 630mg, 640mg, 650mg, 660mg, 670mg, 680mg, 690mg, 70 0 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, or 900 mg), and may be 900 mg or less (e.g., 890 mg, 880 mg, 870 mg, 860 mg, 850 mg, 840 mg, 830 mg, 820 mg, 810 mg, 800 mg, 790 mg, 780 mg, 770 mg, 760 mg, 750 mg, 740 mg, 730 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 810 mg, 820 mg, 830 mg, 840 mg, 850 mg, 860 mg, 870 mg, 880 mg, 890 mg, or 900 mg). 0mg, 710mg, 700mg, 690mg, 680mg, 670mg, 660mg, 650mg, 640mg, 630mg, 620mg, 610mg, 600mg, 590mg, 580mg, 570mg, 560mg, 550mg, 540mg, 530mg, 520mg, 5 10mg, 500mg, 490mg, 480mg, 470mg, 460mg, 450mg, 440mg, 430mg, 420mg, 410mg, 400mg, 390mg, 380mg, 370mg, 360mg, 350mg, 340mg, 330mg, 320mg, 310mg,The amount of hydroxybenzoate may be 300 mg, 290 mg, 280 mg, 270 mg, 260 mg, 250 mg, 240 mg, 230 mg, 220 mg, 210 mg, 200 mg, 190 mg, 180 mg, 170 mg, 160 mg, 150 mg, 140 mg, 130 mg, 120 mg, 110 mg, 100 mg, 90 mg, 80 mg, 70 mg, 60 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg or less). In certain embodiments, the pharmaceutical composition comprises a total protein amount of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, or about 170 mg (e.g., as determined by a Bradford assay or by a BSA assay). mg, about 170mg, about 180mg, about 190mg, about 200mg, about 210mg, about 220mg, about 230mg, about 240mg, about 250mg, about 260mg, about 270mg, about 280mg, about 290mg, about 300mg, about 310mg, about 320mg, about 330mg, about 340mg, about 350mg, about 360mg, about 370mg, about 380mg, about 390mg, about 400mg, about 410m g, about 420mg, about 430mg, about 440mg, about 450mg, about 460mg, about 470mg, about 480mg, about 490mg, about 500mg, about 510mg, about 520mg, about 530mg, about 5 40mg, about 550mg, about 560mg, about 570mg, about 580mg, about 590mg, about 600mg, about 610mg, about 620mg, about 630mg, about 640mg, about 650mg, about 660mg , about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, or about 900 mg.

[0026] In some embodiments, the pharmaceutical composition can have a total amount of Prevotella bacteria of the genus of at least 5 mg (e.g., at least 6 mg, at least 7 mg, at least 8 mg, at least 9 mg, at least 10 mg, at least 11 mg, at least 12 mg, at least 13 mg, at least 14 mg, at least 15 mg, at least 16 mg, at least 17 mg, at least 18 mg, at least 19 mg, or at least 20 mg) and can have an amount of 20 mg or less (e.g., 19 mg or less, 18 mg or less, 17 mg or less, 16 mg or less, 15 mg or less, 14 mg or less, 13 mg or less, 12 mg or less, 11 mg or less, 10 mg or less, 9 mg or less, 8 mg or less, 7 mg or less, 6 mg or less, 5 mg) (e.g., as determined by a Bradford assay or by a BSA assay). In some embodiments, the pharmaceutical composition may have a total amount of Prevotella genus bacteria of about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, or about 20 mg (e.g., as determined by a Bradford assay or by a BSA assay).

[0027] In certain embodiments, the pharmaceutical composition (e.g., a total dose of the composition administered once or twice daily) contains at least 1 x 10 10 Total cells (e.g., at least 1 x 10 10 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 10 Total cells, at least 7 x 10 10 Total cells, at least 8 x 10 10 Total cells, at least 9 x 10 10 Total cells, at least 1 x 10 11In some embodiments, the pharmaceutical composition comprises 9 x 10 Prevotella bacteria. 11 0.01 or less total cells (e.g., 1 x 10 10 Total cells, 2 x 10 or less 10 Total cells less than 3 x 10 10 Total cells, 4 x 10 or less 10 Total cells, 5 x 10 or less 10 Total cells, 6 x 10 or less 10 Total cells, 7 x 10 or less 10 Total cells, 8 x 10 or less 10 Total cells, 9 x 10 or less 10 Total cells less than 1 x 10 11 Total cells, 2 x 10 or less 11 Total cells less than 3 x 10 11 Total cells, 4 x 10 or less 11 Total cells, 5 x 10 or less 11 Total cells, 6 x 10 or less 11 Total cells, 7 x 10 or less 11 Total cells, 8 x 10 or less 11 In some embodiments, the pharmaceutical composition comprises about 6 x 10 total cells of Prevotella bacteria. 9 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 10 In some embodiments, the pharmaceutical composition comprises about 8 x 10 total cells of Prevotella bacteria. 10 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 11 In some embodiments, the pharmaceutical composition comprises about 3.2 x 10 total cells of Prevotella bacteria. 11 In some embodiments, the pharmaceutical composition comprises about 8 x 10 total cells of Prevotella bacteria. 11 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 10 pieces~approx. 8×10 11In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 10 pieces ~ approx. 1.6×10 11 In some embodiments, the pharmaceutical composition comprises about 8 x 10 total cells of Prevotella bacteria. 10 pieces~approx. 8×10 11 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 11 pieces~approx. 8×10 11 Contains a total of 100 cells of Prevotella bacteria.

[0028] In certain embodiments, provided herein are solid dosage forms comprising Prevotella bacteria. In some embodiments, the solid dosage forms comprise an enteric coating. In some embodiments, the solid dosage forms are capsules, e.g., enteric-coated capsules. In some embodiments, each capsule contains about 8 x 10 10 In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered to a subject, e.g., once or twice daily. In some embodiments, 1 capsule (e.g., about 8 x 10 10 In some embodiments, two capsules (e.g., each containing about 8 x 10 total cells) are administered to a subject, e.g., once or twice daily. 10 In some embodiments, four capsules (e.g., each containing about 8 x 10 total cells) are administered to a subject, e.g., once or twice daily. 10 In some embodiments, 10 capsules (e.g., each containing about 8 x 10 total cells) are administered to a subject, e.g., once or twice daily. 10 The capsules (containing 100 total cells) are administered to a subject, for example, once or twice daily. In some embodiments, the Prevotella bacteria in the capsules are freeze-dried (e.g., into a powder).

[0029] In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated tablet. In some embodiments, the capsule contains about 8 x 10 10 In some embodiments, the capsule contains about 1.6 x 10 total cells of Prevotella bacteria (e.g., a total dose of one capsule or multiple capsules). 11 In some embodiments, the capsule contains about 3.2 x 10 total cells of Prevotella bacteria (e.g., a total dose of one capsule or multiple capsules). 11 In some embodiments, the capsule contains about 8 x 10 total cells of Prevotella bacteria (e.g., a total dose of one capsule or multiple capsules). 11 In some embodiments, the Prevotella bacteria in the capsules are lyophilized (e.g., into a powder).

[0030] 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 has a diameter of 5 mm to 17 mm. In some embodiments, the tablet has a diameter of about 8 x 10 10 In some embodiments, the tablet contains about 1.6 x 10 total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). 11 In some embodiments, the tablet contains about 3.2 x 10 total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). 11 In some embodiments, the tablet contains about 8 x 10 total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). 11In some embodiments, the Prevotella bacteria in the tablet comprises 0.05% total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[0031] In some embodiments, the solid dosage form comprises mini-tablets. In some embodiments, the mini-tablets are enteric coated. In some embodiments, the mini-tablets are 1 mm to 4 mm in diameter. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) are 1 mm mini-tablets, 1.5 mm mini-tablets, 2 mm mini-tablets, 3 mm mini-tablets, or 4 mm mini-tablets. In some embodiments, the solid dosage form is about 8 x 10 10 In some embodiments, the solid dosage form comprises a mini-tablet containing about 1.6 x 10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). 11 In some embodiments, the solid dosage form comprises a mini-tablet containing about 3.2 x 10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). 11 In some embodiments, the solid dosage form comprises a mini-tablet containing about 8 x 10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). 11 In some embodiments, the mini-tablets comprise a total of 100 cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). In some embodiments, the Prevotella bacteria in the mini-tablets are freeze-dried.

[0032] In some embodiments, the mini-tablets (e.g., enteric-coated mini-tablets) are contained in a capsule. In some embodiments, the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule comprises (e.g., is coated with) a non-enteric coating (e.g., HPMC (hydroxylpropylmethylcellulose) or gelatin). In some embodiments, the capsule comprises a non-enteric coating. In some embodiments, the capsule comprises hydroxylpropylmethylcellulose (HPMC). In some embodiments, the capsule comprises gelatin. In some embodiments, the capsule comprises about 8 x 10 11 Mini-tablets (e.g., enteric-coated mini-tablets) containing 100 whole cells of Prevotella bacteria are contained in a capsule, and optionally, the capsule contains HPMC.

[0033] In some embodiments, pharmaceutical compositions comprising Prevotella bacteria are prepared as a powder (e.g., a powder for resuspension or use in a solid dosage form (e.g., a capsule)), or as a solid dosage form (e.g., a tablet, mini-tablet, capsule, pill, or powder), or a combination of these forms (e.g., mini-tablets contained in a capsule). In certain embodiments, the powder may comprise lyophilized bacteria.

[0034] In certain embodiments of any one of the aspects disclosed herein, the pharmaceutical composition is formulated as a solid dosage form. In some embodiments, the pharmaceutical composition has a dosage form selected from a tablet, a capsule, a mini-tablet, a powder, or a combination thereof. In some embodiments, the pharmaceutical composition is formulated as a suspension (e.g., a suspension in PBS). In some embodiments, the pharmaceutical composition is formulated for oral, intravenous, subcutaneous, intradermal, and / or intraperitoneal administration. In some embodiments, the pharmaceutical composition is formulated for oral administration.

[0035] In some embodiments, the pharmaceutical composition comprises lyophilized Prevotella bacteria. In certain embodiments, the lyophilized Prevotella bacteria are formulated into a solid dosage form, such as a tablet, mini-tablet, capsule, pill, or powder. In some embodiments, the lyophilized Prevotella bacteria are contained in a capsule. In some embodiments, the lyophilized Prevotella bacteria are resuspended in a solution.

[0036] In certain embodiments, provided herein is a method for treating a pulmonary arthritis, comprising administering to a patient a therapeutically effective amount of T H A method of treating a subject having a 2-mediated condition, comprising administering to the subject a pharmaceutical composition described herein.

[0037] In certain embodiments, provided herein is a method of treating a subject having atopic dermatitis, comprising administering to the subject a pharmaceutical composition described herein.

[0038] In certain embodiments, provided herein is a method of treating a subject with a food allergy, comprising administering to the subject a pharmaceutical composition described herein.

[0039] In some embodiments, the methods provided herein further comprise administering to the subject an antibiotic. In some embodiments, the methods further comprise administering to the subject one or more other treatments for the condition. In some embodiments, the methods further comprise administering another therapeutic bacteria. [Brief explanation of the drawings]

[0040] [Figure 1A]FIG. 11 is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling 8 hours after FITC ear challenge in a contact hypersensitivity model using FITC (ordinary one-way ANOVA; p<0.001 for dexamethasone; p:0.0031 for P. histicola). [Figure 1B-1] 1 is a series of graphs showing that Prevotella histicola treatment reduced gene expression of Il4, Il5, Il33, Il17a, Il1b, and Tslp in the ear. [Figure 1B-2] 1 is a series of graphs showing that Prevotella histicola treatment reduced gene expression of Il4, Il5, Il33, Il17a, Il1b, and Tslp in the ear. [Figure 2] FIG. 1 is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling 8 hours after FITC ear challenge in a contact hypersensitivity model using FITC (ordinary one-way ANOVA; strain 1 is a strain from another species of Prevotella, and strain 2 is a strain from a different genus than Prevotella). [Figure 3A] Figure 1 shows the study design of a model of atopic dermatitis-associated food allergy. [Figure 3B]FIG. 1 is a graph showing that oral administration of Prevotella histicola significantly reduced ear inflammation in an atopic dermatitis-associated food allergy model using an ovalbumin (OVA) food allergen model (ordinary one-way ANOVA; p: 0.0009 for tofacitinib; p<0.0001 for P. histicola; p: 0.0047 for strain B; strain A is a strain from a different genus than Prevotella, and strain B is a different strain of Prevotella histicola). [Figure 3C] 1 is a pair of graphs showing IgG1 and IgE levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. (Strain A is a strain from a different genus than Prevotella, and strain B is another strain of Prevotella histicola.) [Figure 3D-1] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. [Figure 3D-2] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. [Figure 3D-3] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. [Figure 3D-4] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. [Figure 3D-5] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. [Figure 3D-6] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, IL-31, and IL-33 levels in mice administered vehicle, tofacitinib, Prevotella histicola, or two other bacterial species ("Strain A" and "Strain B") in an atopic dermatitis-associated food allergy model using ovalbumin (OVA) food allergen. [Figure 4A] Figure 1 shows the study design of a mouse model to test an atopic dermatitis-associated food allergy model using ovalbumin (OVA) or CPE (whole peanut extract) as food allergens. [Figure 4B] This graph shows that oral administration of Prevotella histicola significantly reduced ear inflammation in both atopic dermatitis-associated food allergy models using OVA and atopic dermatitis-associated food allergy models using peanut allergen (CPE) (ordinary one-way ANOVA; p: <0.0001 for tofacitinib; p: 0.0024 for anti-IL-4; p: 0.0163 for strain A; p: <0.0001 for P. histicola (OVA group); p: <0.0001 for CPE group (vehicle vs. P. histicola); strain A is a strain from a different genus than Prevotella). [Figure 4C] 1 is a pair of graphs showing anti-OVA IgG1 and anti-OVA IgE levels in mice administered vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in an atopic dermatitis-associated food allergy model using an ovalbumin (OVA) food allergen model (strain A is a strain from a different genus than Prevotella). [Figure 4D-1] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, and IL-31 levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in a contact hypersensitivity model using peanut allergen (CPE), ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4D-2]1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, and IL-31 levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in a contact hypersensitivity model using peanut allergen (CPE), ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4D-3] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, and IL-31 levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in a contact hypersensitivity model using peanut allergen (CPE), ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4D-4] 1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, and IL-31 levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in a contact hypersensitivity model using peanut allergen (CPE), ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4D-5]1 is a series of graphs showing IL-4, IL-5, IL-13, IL-10, and IL-31 levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in a contact hypersensitivity model using peanut allergen (CPE), ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4E-1] 1 is a series of graphs showing ear IL-4 RNA levels, IL-5 RNA levels, TSLP RNA levels, CCR4 RNA levels, and IL-19 RNA levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in an atopic dermatitis-associated food allergy model using peanut allergen (CPE) as the food allergen, ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4E-2]1 is a series of graphs showing ear IL-4 RNA levels, IL-5 RNA levels, TSLP RNA levels, CCR4 RNA levels, and IL-19 RNA levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in an atopic dermatitis-associated food allergy model using peanut allergen (CPE) as the food allergen, ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 4E-3] 1 is a series of graphs showing ear IL-4 RNA levels, IL-5 RNA levels, TSLP RNA levels, CCR4 RNA levels, and IL-19 RNA levels in mice treated with vehicle, tofacitinib, anti-IL-4, Prevotella histicola, or another bacterial species ("strain A") in an atopic dermatitis-associated food allergy model using peanut allergen (CPE) as the food allergen, ovalbumin (OVA) food allergen, and vehicle, and in an atopic dermatitis-associated food allergy model using Prevotella histicola (strain A is a strain from a different genus than Prevotella). [Figure 5] MC903 model of induction of type 2 dermatitis and food allergy. [Figure 6A] The study design of the skin sensitization peanut allergy model is shown. [Figure 6B] The study design of the skin sensitization peanut allergy model is shown. [Figure 6C] The study design of the skin sensitization peanut allergy model is shown. [Figure 6D]1 is a graph showing that oral administration of Prevotella histicola significantly reduced ear swelling in a skin-sensitized peanut allergy model. [Figure 6E] 1 is a pair of graphs showing total IgE and anti-peanut IgE levels on the day of challenge in mice administered vehicle, tofacitinib (“Tofa”), or Prevotella histicola in a skin-sensitization peanut allergy model. [Figure 6F] 1 is a pair of graphs showing total IgG1 and anti-peanut IgG1 levels on the day of challenge in mice administered vehicle, tofacitinib (“tofa”), or Prevotella histicola in a skin sensitization peanut allergy model. [Figure 6G] 1 is a pair of graphs showing total IgE and anti-peanut IgE levels at two weeks post-challenge in mice administered vehicle, tofacitinib (“Tofa”), or Prevotella histicola in a skin-sensitization peanut allergy model. [Figure 6H] 1 is a pair of graphs showing total IgG1 and anti-peanut IgG1 levels at two weeks post-challenge in mice administered vehicle, tofacitinib (“Tofa”), or Prevotella histicola in a skin-sensitization peanut allergy model. [Figure 6I] 1 is a pair of graphs showing total IgA and anti-peanut IgGA levels at two weeks post-challenge in mice administered vehicle, tofacitinib (“Tofa”), or Prevotella histicola in a skin-sensitization peanut allergy model. [Figure 7A] FIG. 1 is a schematic diagram showing the experimental design of the FITC-CHS model. [Figure 7B-1]1 is a series of graphs showing IL-13, IL-4, IL-5, IL-31, and IL-33 levels in ex vivo restimulated mesenteric lymph node (mLN) cells from mice administered vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model. [Figure 7B-2] 1 is a series of graphs showing IL-13, IL-4, IL-5, IL-31, and IL-33 levels in ex vivo restimulated mesenteric lymph node (mLN) cells from mice administered vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model. [Figure 7C-1] 1 is a series of graphs showing IL-13, IL-4, IL-5, IL-31, and IL-33 levels in ex vivo restimulated ear-draining cervical lymph node (cLN) cells from mice administered vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model. [Figure 7C-2] 1 is a series of graphs showing IL-13, IL-4, IL-5, IL-31, and IL-33 levels in ex vivo restimulated ear-draining cervical lymph node (cLN) cells from mice administered vehicle, dexamethasone, or Prevotella histicola in the FITC-CHS model. [Figure 8A] FIG. 1 is a schematic diagram showing the experimental design of an atopic dermatitis model using MC903. [Figure 8B]FIG. 1 is a pair of graphs showing ear measurements over time (left panel) and ear inflammation at day 14 (right panel) in mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. [Figure 8C-1] 1 is a series of graphs showing transcript levels of Tslp, Il5, Il31, Il4, Ccl19, and Ccr4 in ear tissue from mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. [Figure 8C-2] 1 is a series of graphs showing transcript levels of Tslp, Il5, Il31, Il4, Ccl19, and Ccr4 in ear tissue from mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. [Figure 8D] 1 is a graph showing mast cell-related gene (Mcpt1) transcript levels in the jejunum from mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. [Figure 8E] 1 is a graph showing IL-10 levels in the mesenteric lymph nodes (left panel) and spleens (right panel) in mice treated with vehicle, tofacitinib, or Prevotella histicola in an atopic dermatitis model using MC903. DETAILED DESCRIPTION OF THE INVENTION

[0041] As disclosed herein, pharmaceutical compositions comprising bacteria of the genus Prevotella have a therapeutic effect and are effective against one or more T. HSuch T-cell receptor agonists are useful in the treatment or prevention (i.e., treatment, prevention, or both treatment and prevention) of T-cell receptor agonists. H 2-mediated conditions include, but are not limited to, allergic rhinitis, asthma, atopic dermatitis, urticaria, angioedema, allergies (e.g., food allergies, insect-induced allergies, drug allergies), anaphylaxis, and eosinophilia. The pharmaceutical composition may comprise the Prevotella histicola bacterium.

[0042] definition "Adjuvant" or "adjuvant therapy" refers broadly to an agent that affects the immunological or physiological response of a subject (e.g., a human). For example, an adjuvant may increase the presence of an antigen over time or to a desired area, aid in antigen uptake by antigen-presenting cells, activate macrophages and lymphocytes, and support cytokine production. By altering the immune response, an adjuvant may allow for lower doses of an immunointeractive agent, thereby increasing the efficacy or safety of a particular dose of an immunointeractive agent. For example, an adjuvant may prevent T-cell exhaustion, thereby increasing the efficacy or safety of a particular immunointeractive agent.

[0043] "Administration" refers broadly to the route of administration of a composition (e.g., a pharmaceutical composition) to a subject. Examples of routes of administration include oral administration, rectal administration, topical administration, inhalation (nasal), or injection. Administration by injection includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. The pharmaceutical compositions described herein can be administered in any form by any effective route, including, but not limited to, oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), intradermal, intraocular, nasal (intranasal), topical, parenteral, e.g., aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, rectal, vaginal, intraarterial, and intrathecal, transmucosal (e.g., sublingual, lingual, buccal, urethral, ​​vaginal (e.g., vaginal and perivaginal), implant, intravesical, pulmonary, intraduodenal, intragastric, and intrabronchial. In preferred embodiments, the pharmaceutical compositions described herein are administered orally, rectally, topically, intravesically, by injection into or near a draining lymph node, intravenously, by inhalation or aerosol, or subcutaneously. In another preferred embodiment, the pharmaceutical compositions described herein are administered orally or intravenously.

[0044] As used herein, the term "antibody" can refer to both intact antibodies and antigen-binding fragments thereof. Intact antibodies are glycoproteins comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain contains a heavy chain variable region (herein referred to as V H Each light chain comprises a light chain variable region (abbreviated herein as V) and a heavy chain constant region. L and the light chain constant region. H and V L The region can be further subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). H and V Lis composed of three CDRs and four FRs, arranged in the following order from the amino terminus to the carboxy terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with an antigen. The term "antibody" includes, for example, monoclonal antibodies, polyclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, multispecific antibodies (e.g., bispecific antibodies), single-chain antibodies, and antigen-binding antibody fragments.

[0045] As used herein, the terms "antigen-binding fragment" and "antigen-binding portion" of an antibody refer to one or more fragments of an antibody that retain the ability to bind to an antigen. Examples of binding fragments encompassed by the term "antigen-binding fragment" of an antibody include Fab, Fab', F(ab')2, Fv, scFv, disulfide-linked Fv, Fd, diabodies, single-chain antibodies, NANOBODIES®, isolated CDRH3, and other antibody fragments that retain at least a portion of the variable region of an intact antibody. These antibody fragments can be obtained using conventional recombinant and / or enzymatic techniques and can be screened for antigen binding in the same manner as intact antibodies.

[0046] "Carbohydrate" refers to a sugar or a polymer of sugars. The terms "saccharide," "polysaccharide," "carbohydrate," and "oligosaccharide" may be used interchangeably. Most carbohydrates are aldehydes or ketones with many hydroxyl groups (usually one hydroxyl group on each carbon atom of the molecule). Carbohydrates generally have the molecular formula C n H 2n O nCarbohydrates can be monosaccharides, disaccharides, trisaccharides, oligosaccharides, or polysaccharides. The most basic carbohydrates are monosaccharides, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose. Disaccharides are two monosaccharides linked together. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose. Oligosaccharides typically contain three to six monosaccharide units (e.g., raffinose, stachyose), while polysaccharides contain six or more monosaccharide units. Exemplary polysaccharides include starch, glycogen, and cellulose. Carbohydrates can include modified sugar units, such as 2'-deoxyribose, where the hydroxyl group has been removed; 2'-fluororibose, where the hydroxyl group has been replaced with fluorine; or N-acetylglucosamine; nitrogen-containing forms of glucose (e.g., 2-fluororibose, deoxyribose, and hexose). Carbohydrates can exist in many different forms, including conformational isomers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.

[0047] "Cell enrichment" refers broadly to the influx or expansion of cells in an environment that are substantially absent from the environment prior to administration of the composition (e.g., pharmaceutical composition) and that are absent from the composition itself. Cells that enrich the environment include immune cells, stromal cells, bacterial cells, and fungal cells.

[0048] "Clade" refers to a member of an OUR or phylogenetic tree that is located downstream of a statistically significant node in the phylogenetic tree. A clade comprises a set of terminal leaves in a phylogenetic tree that are distinct monophyletic evolutionary units and share some degree of sequence similarity.

[0049] A "combination" of microorganisms (e.g., bacteria) from two or more microbial strains includes the physical coexistence of the microorganisms, either in the same material or product, or in physically connected products, as well as the temporal co-administration or co-localization of the two or more strains. In some embodiments, one of the strains is from the Prevotella bacterium, e.g., Prevotella histicola bacterium.

[0050] The terms "reduce" or "deplete" refer to a change in a condition where the difference is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1 / 100, 1 / 1000, 1 / 100,000, 1 / 1000,000, or undetectable after treatment compared to the condition before treatment, as appropriate. Characteristics that may be reduced include the number of immune cells, bacterial cells, stromal cells, myeloid-derived suppressor cells, fibroblasts, metabolites; cytokine levels; or another physical parameter, such as ear thickness (e.g., ear thickness in a DTH animal model) or tumor size (e.g., tumor size in an animal tumor model).

[0051] The term "ecological consortium" refers to a group of bacteria that exchange metabolites and actively co-regulate each other, as opposed to two bacteria that induce host synergy by activating complementary host pathways for improved efficacy.

[0052] As used herein, "engineered bacteria" refers to any bacteria that have been genetically altered from their natural state by human activity, and any progeny of such bacteria. Engineered bacteria include, for example, the products of targeted gene modification, random mutagenesis screening, and directed evolution.

[0053] The term "epitope" refers to a protein determinant capable of specific binding to an antibody or T-cell receptor. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains. A particular epitope can be defined by the specific amino acid sequence to which an antibody can bind.

[0054] The term "gene" is used broadly to refer to any nucleic acid associated with a biological function. The term "gene" applies to a specific genomic sequence and to the cDNA or mRNA encoded by that genomic sequence.

[0055] "Identity" between the nucleic acid sequences of two nucleic acid molecules can be determined as a percentage of identity using known computer algorithms, such as the "FASTA" program using default parameters as described in, for example, Pearson et al. (1988) Proc. Natl. Acad. Sci. USA 85:2444 (other programs include the GCG program package (Devereux, J., et al., Nucleic Acids Research 12(I):387 (1984)), BLASTP, BLASTN, FASTA Atschul, S. F., et al., J. Molec. Biol. 215:403 (1990); Guide to Huge Computers, Martin J. Bishop, ed., Academic Press, San Diego, 1994, and Carillo et al. (1988) SIAM J Applied Math. 48:1073). For example, identity can be determined using the BLAST function of the National Center for Biotechnology Information database. Other commercially or publicly available programs include the DNAStar "MegAlign" program (Madison, Wis.) and the University of Wisconsin Genetics Computer Group (UWG) "Gap" program (Madison, Wis.).

[0056] "Immunotherapy" refers to treatments that use a subject's immune system to treat a disease (e.g., an immune disease, an inflammatory disease, a metabolic disease, or cancer), and includes, for example, checkpoint inhibitors, cancer vaccines, cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.

[0057] The term "increase" refers to a change in a post-treatment state, as compared to the pre-treatment state, that is 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 greater than 10^7-fold, as appropriate. Possible increased characteristics include the number of immune cells, bacterial cells, stromal cells, myeloid-derived suppressor cells, fibroblasts, metabolites; cytokine levels; or another physical parameter, such as ear thickness (e.g., ear thickness in a DTH animal model) or tumor size (e.g., tumor size in an animal tumor model).

[0058] "Innate immune agonists" or "immunoadjuvants" are small molecules, proteins, or other agents that specifically target innate immune receptors (e.g., Toll-like receptors (TLRs), NOD receptors, RLPs, C-type lectin receptors, STING-cGAS pathway components, inflammasome complexes). For example, LPS is a bacterially derived or synthetic TLR-4 agonist, and aluminum may be used as an immunostimulatory adjuvant. Immune adjuvants are a specific class of broader adjuvants or adjuvant therapies. Examples of STING agonists include, but are not limited to, 2'3'-cGAMP, 3'3'-cGAMP, c-di-AMP, c-di-GMP, 2'2'-cGAMP, and 2'3'-cGAM(PS)2(Rp / Sp) (the Rp,Sp-isomer of the bis-phosphorothioate analog of 2'3'-cGAMP). Examples of TLR agonists include, but are not limited to, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, and TLR11. Examples of NOD agonists include, but are not limited to, N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide (MDP)), gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), and desmuramyl peptide (DMP).

[0059] The "internal transcribed spacer" (ITS) is a non-functional segment of RNA located between structural ribosomal RNAs (rRNAs) on a common precursor transcript, often used to identify eukaryotic species in certain fungi. Fungal rRNAs, which form the core of the ribosome, are transcribed as signal genes and consist of the 8S, 5.8S, and 28S regions, with ITSs 4 and 5 located between the 8S and 5.8S regions, and between the 5.8S and 28S regions, respectively. These two intercistronic segments, between the 18S and 5.8S regions and between the 5.8S and 28S regions, are removed by splicing and contain significant variation between species for barcoding purposes, as previously described (Schoch et al., Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. PNAS 109:6241-6246. 2012). Although 18S rDNA is traditionally used for phylogenetic reconstruction, the ITS can serve this function because it contains hypervariable regions that are generally highly conserved but possess sufficient nucleotide diversity to distinguish most fungal genera and species.

[0060] The terms "isolated" or "enriched" include microorganisms or other entities or substances that are (1) isolated from at least some of the components with which they were originally associated when produced (whether in nature or an experimental setting) and / or (2) produced, prepared, purified, and / or manufactured by the hand of man. Isolated microorganisms can be isolated from at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more of the other components with which they were originally associated. In some embodiments, isolated microorganisms are greater than about 80%, greater than about 85%, greater than about 90%, greater than about 91%, greater than about 92%, greater than about 93%, greater than about 94%, greater than about 95%, greater than about 96%, greater than about 97%, greater than about 98%, greater than about 99%, or greater than about 99% pure, e.g., substantially free of other components. The terms "purify," "purifying," and "purified" refer to a microorganism or other material that has been isolated from at least some of the components that were associated with it when it was originally produced or generated (e.g., whether in a natural or experimental setting), or any time after initial production. A microorganism or population of microorganisms can be considered purified from the material, environment, etc. containing the microorganism or population of microorganisms if it is isolated at or after production; a purified microorganism or population of microorganisms may contain up to about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more than 90% other materials and still be considered "isolated." In some embodiments, a purified microorganism or population of microorganisms is about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or greater than about 99% pure. In the case of the microbial compositions provided herein, one or more microbial species present in the composition can be purified away from one or more other microorganisms produced and / or present in the material or environment containing the microbial species. Microbial compositions and their microbial components are generally purified from residual habitat products.

[0061] As used herein, "lipid" includes any form of fatty acid, such as fats, oils, triglycerides, cholesterol, phospholipids, free fatty acids, etc. Fats, oils, and fatty acids can be saturated, unsaturated (cis or trans), or partially unsaturated (cis or trans).

[0062] The term "LPS mutant or lipopolysaccharide mutant" broadly refers to the selection of bacteria lacking LPS. LPS loss can result from mutations or disruptions in genes involved in lipid A biosynthesis, such as lpxA, lpxC, and lpxD. Bacteria containing LPS mutations can be resistant to aminoglycosides and polymyxins (polymyxin B and colistin).

[0063] "Metabolite," as used herein, refers to any and all molecular compounds, compositions, molecules, ions, cofactors, catalysts, or nutrients that are used as substrates in any cellular or microbial metabolic reaction, or that are obtained as products from any cellular or microbial metabolic reaction.

[0064] "Microorganism" refers to natural or engineered organisms characterized by archaea, parasites, bacteria, fungi, microalgae, protozoa, and the developmental or life cycle stages associated with these organisms (e.g., vegetative, sporulent (e.g., sporulation, dormancy, and germination), latent, biofilm). In some embodiments, the microorganism is a bacterium. Examples of gut microbes include: Actinomyces graevenitzii, Actinomyces odontolyticus, Akkermansia muciniphila, Bacteroides caccae, Bacteroides fragilis, Bacteroides putredinis, Bacteroides thetaiotaomicron, Bacteroides vultagus, Bifidobacterium adolescentis, and Bifidobacterium bifidum. bifidum, Bilophila wadsworthia, Blautia, Butyrivibrio, Campylobacter gracilis, Clostridia cluster III, Clostridia cluster IV, Clostridia cluster IX (Acidaminococcaceae group), Clostridia cluster XI, Clostridia cluster XIII (Peptostreptococcusgroup), Clostridia cluster XIV, Clostridia cluster XV, Collinsella aerofaciens, Coprococcus, Corynebacterium sunsvallense, Desulfomonas pigra, Dorea formicigenerans, Dorea longicatena, Escherichia coli, Eubacterium hadrum, Eubacterium rectale, Faecalibacteria prausnitz prausnitzii, Gemella, Lactococcus, Lachnospira, Mollicutes cluster XVI, Mollicutes cluster XVIII, Prevotella, Rothia mucilaginosa, Ruminococcus callidus, Ruminococcus gnavus, Ruminococcus torques, and Streptococcus.

[0065] "Microbiome" broadly refers to the microorganisms present on or in a body site of a subject or patient. Microorganisms in a microbiome can include bacteria, viruses, eukaryotic microorganisms, and / or viruses. Individual microorganisms in a microbiome can be metabolically active, dormant, latent, or exist as spores, planktonically, or in biofilms, or can be present in the microbiome persistently or transiently. The microbiome can be a commensal or healthy microbiome, or a diseased microbiome. The microbiome can be indigenous to a subject or patient, or components of the microbiome can be modulated, introduced, or depleted due to changes in health or treatment conditions (e.g., antibiotic treatment, exposure to various microorganisms). In some aspects, the microbiome occurs at a mucosal surface. In some aspects, the microbiome is the gut microbiome.

[0066] A "microbiome profile" or "microbiome signature" of a tissue or sample refers to at least a partial characterization of the bacterial makeup of the microbiome. In some embodiments, the microbiome profile indicates the presence or absence of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more bacterial strains in the microbiome.

[0067] "Modified" with respect to bacteria broadly refers to bacteria that have undergone a change from the wild type. Bacterial modifications can occur through manipulation of the bacteria. Examples of bacterial modifications include genetic modifications, gene expression modifications, phenotypic modifications, formulation modifications, chemical modifications, and dosage or concentration. Examples of improved properties are described throughout this specification and include, for example, attenuation, auxotrophy, homing, or antigenicity. Phenotypic modifications can include, for example, growing the bacteria in a medium that modifies the bacterial phenotype to increase or decrease virulence.

[0068] "Operational Taxonomic Unit" and "OUU" refer to terminal leaves in a phylogenetic tree and are defined by a nucleic acid sequence (e.g., an entire genome or a specific gene sequence) and all sequences that share sequence identity to this nucleic acid sequence at the species level. In some embodiments, this specific gene sequence can be a portion of the 16S sequence or 16S sequence. In other embodiments, the entire genomes of two entities are sequenced and compared. In another embodiment, selected regions, specific genes, or sets of genes, such as multilocus sequence tags (MLST), can be genetically compared. In the case of 16S, OTUs that share 97% or more average nucleotide identity across the entire 16S or a portion of the 16S variable region are considered to be identical OUTs. See, e.g., Claesson MJ, Wang Q, O'Sullivan O, Greene-Diniz R, Cole JR, Ross RP, and O'Toole PW. 2010. Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res 38:e200. Konstantinidis KT, Ramette A, and Tiedje JM. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361:1929-1940. In the case of complete genomes, MLST, or specific genes or sets of genes other than 16S, OTUs that share 95% or more average nucleotide identity are considered to be the same OTU.See, for example, Achtman M, and Wagner M. 2008. Microbial diversity and the genetic nature of microbial species. Nat. Rev. Microbiol. 6:431-440. Konstantinidis KT, Ramette A, and Tiedje JM. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361:1929-1940. OTUs are often defined by comparing sequences between organisms. Generally, sequences with less than 95% sequence identity are not considered to form part of the same OTU. OTUs can also be characterized by any combination of nucleotide markers or nucleotide genes, particularly highly conserved genes (e.g., "housekeeping" genes), or combinations thereof. Provided herein are operational taxonomic units (OTUs) that are taxonomically assigned to, for example, genera, species, and clades.

[0069] As used herein, a gene is "overexpressed" in a bacterium if it is expressed at a higher level in an engineered bacterium under at least some conditions than it is expressed by a wild-type bacterium of the same species under the same conditions. Similarly, a gene is "underexpressed" in a bacterium if it is expressed at a lower level in an engineered bacterium under at least some conditions than it is expressed by a wild-type bacterium of the same species under the same conditions.

[0070] The terms "polynucleotide" and "nucleic acid" are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or their analogs. Polynucleotides can have any three-dimensional structure and can perform any function. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci defined by linkage analysis, exons, introns, messenger RNA (mRNA), microRNA (miRNA), silencing RNA (siRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. Polynucleotides can contain modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can be imparted before or after assembly of the polymer. Polynucleotides may be further modified, such as by conjugation with a labeling component. In all nucleic acid sequences provided herein, U nucleotides are interchangeable with T nucleotides.

[0071] As used herein, a "biomarker" refers to a H These include molecules (e.g., mRNA or proteins) whose levels are increased or decreased due to pathways mediated by T2. By way of example, the level of one or more such biomarkers may be increased or decreased in a subject relative to its level in a healthy subject. H

[0001] Some examples of such protein biomarkers include interleukin-4, interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-31, interleukin-33, thymic stromal lymphopoietin, immunoglobulin G1, immunoglobulin E, immunoglobulin A, and combinations thereof. Some examples of such mRNA biomarkers include interleukin-4, interleukin-5, interleukin-13, interleukin-19, interleukin-21, interleukin-31, interleukin-33, thymic stromal lymphopoietin, and combinations thereof.

[0072] As used herein, a substance is "pure" if it is substantially free of other components. The terms "purify," "purifying," and "purified" refer to a Prevotella bacterial preparation or other substance that has been separated from at least some of the components that accompanied it when it was originally produced or generated (e.g., in nature or in an experimental setting) or for any time after initial production. A Prevotella bacterial preparation or composition may be considered purified if it has been isolated from, for example, one or more other bacterial components during or after production; a purified microorganism or population of microorganisms may contain up to about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more than about 90% of other substances and still be considered "purified." In some embodiments, the purified Prevotella bacteria are greater than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or greater than about 99% pure. The Prevotella bacteria composition or preparation may, for example, be purified from residual habitat products.

[0073] As used herein, the term "purified Prevotella bacteria" or "Prevotella bacterial composition" refers to a preparation comprising Prevotella bacteria that has been separated from at least one accompanying substance found in the source material (e.g., separated from at least one other bacterial strain), or that has been separated from any substance that accompanies the Prevotella bacteria in any process used to produce the preparation. The term also refers to a composition that is significantly enriched or concentrated. In some embodiments, the Prevotella bacteria are concentrated 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 100-fold, 1000-fold, 10,000-fold, or more than 10,000-fold. In certain embodiments, the Prevotella bacterial composition can be a pharmaceutical composition.

[0074] "Residual habitat product" refers to material derived from a microbial habitat in or on a subject. For example, a microbial fermentation culture may contain contaminants, such as other strains or forms of microorganisms (e.g., bacteria, viruses, mycoplasma, and / or fungi). For example, microorganisms may live in feces in the digestive tract, on the skin itself, in saliva, in mucus in the respiratory tract, or in secretions of the genitourinary tract (i.e., in biological material associated with the microbial community). Substantially free of residual habitat products means that the microbial composition no longer contains biological material associated with the culture or microbial environment on or in the human or animal subject, and is 100% free, 99% free, 98% free, 97% free, 96% free, or 95% free of any contaminating biological material associated with the microbial community. Residual habitat products may include non-living material (e.g., undigested food) or may contain unwanted microorganisms. Substantially free of residual habitat products can also mean that the microbial composition is free of culture contaminants or detectable cells from humans or animals, and only microbial cells are detectable. In one embodiment, substantially free of residual habitat products can also mean that the microbial composition is free of detectable viral (e.g., bacterial, viral (e.g., phage)) contaminants, fungal contaminants, mycoplasma contaminants. In another embodiment, substantially free of residual habitat products means that the microbial composition is free of 1 x 10 viable cells in the microbial composition compared to microbial cells. -2 %, 1×10 -3 %, 1×10 -4 %, 1×10 -5 %, 1×10 -6 %, 1×10 -7 %, 1×10 -8This means that less than % of the cells are human or animal. There are multiple ways to achieve this purity, but the invention is not limited to any of these. Thus, contamination can be reduced by isolating the desired component through multiple steps of streaking single colonies on solid media until repeated (e.g., but not limited to, two) streaks from a series of single colonies show only single colony morphology. Alternatively, multiple rounds of serial dilutions (e.g., 10-fold serial dilutions) of a single desired cell can be performed. -8 or 10 -9 Dilution of the desired components (e.g., dilution of the desired components) can result in reduced contamination. This can be further confirmed by demonstrating that multiple isolated colonies have similar cytometric and Gram staining behavior. Other methods of confirming adequate purity include genetic analysis (e.g., PCR, DNA sequencing), serological and antigenic analyses, enzymatic and metabolic analyses, and instrumental methods such as flow cytometry with reagents that distinguish the desired components from contaminants.

[0075] As used herein, "specific binding" refers to the ability of an antibody to bind to a predetermined antigen, or the ability of a polypeptide to bind to its predetermined binding partner. Typically, an antibody or polypeptide binds to a specific antigen within about 10 -7 K below M D specifically binds to its given antigen or binding partner with an affinity corresponding to , and is at least 10-fold less, at least 100-fold less, or at least 1000-fold less than the affinity for binding to a nonspecific and unrelated antigen / binding partner (e.g., BSA, casein). D Alternatively, specific binding may more broadly apply to two-component systems in which one component is a protein, lipid, or carbohydrate, or a combination thereof, and specifically binds to a second component that is a protein, lipid, carbohydrate, or a combination thereof.

[0076] A "strain" refers to a member of a bacterial species that possesses genetic characteristics that distinguish it from closely related members of the same bacterial species. Genetic characteristics can be the absence of all or part of at least one gene, the absence of all or part of at least one regulatory region (e.g., promoter, terminator, riboswitch, ribosome binding site), the absence of at least one native plasmid ("cured"), 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 from another species), the presence of at least one mutated regulatory region (e.g., promoter, terminator, riboswitch, ribosome binding site), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or a combination thereof. Genetic characteristics between different strains can be identified by PCR amplification and, optionally, subsequent DNA sequencing of the genomic regions of interest or the entire genome. If one strain (compared to another strain of the same species) gains or loses antibiotic resistance, or gains or loses biosynthetic capabilities (such as auxotrophic strains), the strains can be differentiated by selection with antibiotics or counter-selection with nutrients / metabolites.

[0077] The term "subject" or "patient" refers to any mammal. A subject or patient described as "in need" refers to one in need of disease treatment (or prevention). Mammals (i.e., mammalian animals) include humans, laboratory animals (e.g., primates, rats, mice), farm animals (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents). The subject may be a human. The subject may be a non-human mammal, including, but not limited to, dogs, cats, cows, horses, pigs, donkeys, goats, camels, mice, rats, guinea pigs, sheep, llamas, monkeys, gorillas, or chimpanzees. The subject may be healthy or afflicted with a condition at any stage of development, any of which is caused or opportunistically supported by a condition-associated or causative pathogen, or is at risk of developing the condition or may transmit the condition-associated or causative pathogen to others. In some embodiments, the subject has T H In some embodiments, the subject has a rheumatoid arthritis-mediated condition. In some embodiments, the subject has atopic dermatitis. In some embodiments, the subject has asthma. In some embodiments, the subject has a food allergy. In some embodiments, the subject is receiving treatment for these conditions.

[0078] As used herein, the term "treating" a subject's disease or "treating" a subject having or suspected of having a condition refers to pharmacologically treating a subject (e.g., a pharmaceutical composition), e.g., administering one or more agents (e.g., a pharmaceutical composition), such that at least one symptom of the condition is alleviated or prevented from worsening. Thus, in one embodiment, "treating" refers to, among other things, delaying progression, promoting remission, inducing remission, enhancing remission, accelerating recovery, increasing the effectiveness of or reducing resistance to alternative therapeutic agents, or a combination thereof. In certain embodiments, cancer is treated when a subject experiences, after treatment, a decrease in tumor size, a decrease in tumor number, a decrease in tumor growth, a decrease in cancer metastasis, and / or a decrease in total cancer cell count beyond that expected without treatment.

[0079] bacteria In certain aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising certain bacteria, and methods for using such bacterial compositions (e.g., pharmaceutical compositions) to treat T. H and methods for treating and / or preventing HIV-1 mediated conditions.

[0080] In certain embodiments, the pharmaceutical compositions provided herein comprise bacteria of the genus Prevotella. In some embodiments, the bacteria of the genus Prevotella are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella histicola, Prevotella melanogenica, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivariae salivae, Prevotella stercorea (Prevotellastercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella roescheii The present invention relates to a method for treating bacterial infections, such as bacterial infections caused by bacteria, the bacterial infections caused by bacteria, and the bacterial infections caused by bacteria, such as bacteria, which are selected from the group consisting of: Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludiviens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, Prevotella veroralis, and / or combinations thereof.

[0081] In some embodiments, the bacteria of the genus Prevotella is of the species Prevotella histicola.

[0082] In some embodiments, the bacterium of the genus Prevotella is a strain that comprises at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.1% sequence identity, at least 99.2% sequence identity, at least 99.3% sequence identity, at least 99.4% sequence identity, at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to a nucleotide sequence (e.g., a genome sequence, a 16S sequence, and / or a CRISPR sequence) of Prevotella strain B 50329. In some embodiments, the bacterium of the genus Prevotella is Prevotella strain B 50329 (NRRL Accession No. B 50329). As used herein, the term "Prevotella strain B 50329" includes both the strain deposited under NRRL Accession No. B 50329 and strains cloned from and / or derived from this deposited strain.

[0083] Prevotella histicola strain B can be cultured according to methods known in the art. For example, Prevotella histicola can be grown in ATCC Medium 2722, ATCC Medium 1490, or other media using, for example, the methods disclosed in Caballero et al., 2017, "Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium," Cell Host & Microbe 21:592-602, which is incorporated herein by reference in its entirety.

[0084] In some embodiments, the Prevotella bacteria express one or more proteins listed in Table 1 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or more) and / or is a strain of Prevotella bacteria that includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or more) genes encoding a protein listed in Table 1. In some embodiments, the Prevotella bacterium includes all of the proteins listed in Table 1 and / or all of the genes encoding the proteins listed in Table 1.

[0085] [Table 1]

[0086] Table 2

[0087] Table 3

[0088] Table 4

[0089] Table 5

[0090] Table 6

[0091] Table 7

[0092] Table 8

[0093] Table 9

[0094] Table 10

[0095] Table 11

[0096] Table 12

[0097] In some embodiments, the Prevotella bacteria are capable of expressing one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more) proteins listed in Table 2 and / or the proteins listed in Table 2. In some embodiments, the Prevotella bacterium is a strain of Prevotella bacteria that is free of or substantially free of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more) genes encoding proteins listed in Table 2. In some embodiments, the Prevotella bacterium is free of all of the proteins listed in Table 2 and / or all of the genes encoding the proteins listed in Table 2.

[0098] [Table 13]

[0099] [Table 14]

[0100] [Table 15]

[0101] [Table 16]

[0102] [Table 17]

[0103] [Table 18]

[0104] [Table 19]

[0105] [Table 20]

[0106] [Table 21]

[0107] In some embodiments, the Prevotella bacterium is from a strain of Prevotella bacteria that comprises one or more of the proteins listed in Table 1 and is free or substantially free of one or more proteins listed in Table 2. In some embodiments, the Prevotella bacterium is from a strain of Prevotella bacteria that comprises all of the proteins listed in Table 1 and / or all of the genes encoding the proteins listed in Table 1, and is free of all of the proteins listed in Table 2 and / or all of the genes encoding the proteins listed in Table 2.

[0108] Pharmaceutical Composition In certain embodiments, provided herein are, for example, T Hand a pharmaceutical composition comprising a Prevotella bacterium (e.g., a Prevotella bacterium described herein) for use in a method for treating or preventing a 2-mediated condition (e.g., atopic dermatitis, asthma, and / or allergies). In some embodiments, the Prevotella bacterial composition comprises a Prevotella bacterium and / or a combination of bacterial strains described herein and a pharmaceutically acceptable carrier. In some embodiments, the Prevotella bacterial composition comprises a single Prevotella bacterial strain described herein and a pharmaceutically acceptable carrier.

[0109] In some embodiments, the pharmaceutical composition comprises Prevotella bacteria and one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) bacterial strains or species in addition to, for example, Prevotella. In some embodiments, the pharmaceutical composition comprises Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises lyophilized Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises gamma-irradiated Prevotella bacteria. In some embodiments, the pharmaceutical composition comprises live Prevotella bacteria.

[0110] In some embodiments, to quantify the number of Prevotella bacteria present in a bacterial sample, electron microscopy (e.g., ultrathin cryosection EM) can be used to visualize the bacteria and count their relative numbers. Alternatively, nanoparticle tracking analysis (NTA), Coulter counting, or dynamic light scattering (DLS), or a combination of these techniques, can be used. NTA and Coulter counters count particles and indicate their size. DLS provides particle size distributions but not concentrations. Bacteria often have diameters between 1 and 2 micrometers (um). The full range is 0.2 to 20 um. Coulter count and NTA results can be combined to reveal the number of bacteria in a given sample. Coulter counting reveals the number of particles between 0.7 and 10 um in diameter. For most bacterial samples, a Coulter counter alone can reveal the number of bacteria. For NTA, the Nanosight instrument can be obtained from Malvern Panalytical. For example, the NS300 can visualize and measure particles in suspension with a size range of 10-2000 nm. NTA allows counting the number of particles with diameters of, for example, 50-1000 nm. DLS reveals the distribution of particles with various diameters within the approximate range of 1 nm to 3 μm.

[0111] In some embodiments, Prevotella bacteria can be quantified based on particle number, for example, the total particle number of Prevotella bacteria can be measured using NTA.

[0112] In some embodiments, Prevotella bacteria may be quantified based on total cell count (TCC) (eg, determined by a Coulter counter).

[0113] In some embodiments, Prevotella bacteria may be quantified using a plate count assay (e.g., by making serial dilutions of the bacteria, growing them on an appropriate medium, and then counting the number of colonies).

[0114] In some embodiments, Prevotella bacteria can be quantified based on the amount of protein, lipid, or carbohydrate. For example, the total protein content of a Prevotella bacteria preparation can be measured using a Bradford assay or a BCA assay.

[0115] In some embodiments, the Prevotella bacteria are isolated from one or more other bacterial components, e.g., of a source culture. In some embodiments, the pharmaceutical composition further comprises other bacterial components or strains.

[0116] In certain aspects, provided are pharmaceutical compositions for administration to a subject (e.g., a human subject). In some embodiments, the pharmaceutical compositions are combined with additional active and / or inactive agents to produce a final product, which may be in a single dosage unit or in a multi-dose format.

[0117] In some embodiments, the pharmaceutical composition comprises at least one carbohydrate.

[0118] In some embodiments, the pharmaceutical composition comprises at least one lipid. In some embodiments, the lipid comprises at least one fatty acid selected from the following: 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), octadecenoic acid (18:4), octadecenoic acid (18:5), octadecenoic acid (18:6), octadecenoic acid (18:7), octadecenoic acid (18:8), octadecenoic acid (18:9), octadecenoic acid (18:10), octadecenoic acid (18:11), octadecenoic acid (18:12), octadecenoic acid (18:13), octadecenoic acid (18:14), octadecenoic acid (18:15), octadecenoic acid (18:16), octadecenoic acid (18:17), octadecenoic acid (18:18), octadecenoic acid (18:19), octadecenoic acid (18:19), octadecenoic acid (18:19), octadecenoic acid (18:11), octadecenoic acid (18:12), octadecenoic acid (18:13), octadecenoic acid (18:14), octadecenoic acid (18:15), octadecenoic acid (18:16), octadecenoic acid (18:17), octadecenoic acid (18:18), octadecenoic acid (18:19), oc Tadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20:1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EPA), docosanoic acid (22:0), docosenoic acid (22:1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and tetracosanoic acid (24:0).

[0119] In some embodiments, the pharmaceutical composition comprises at least one supplemental mineral or mineral source. Examples of minerals include, but are not limited to, chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the above minerals include soluble mineral salts, sparingly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals (e.g., carbonyl minerals), and reduced minerals, and combinations thereof.

[0120] In some embodiments, the pharmaceutical composition includes at least one supplemental vitamin. The at least one vitamin can be a fat-soluble or water-soluble vitamin. Suitable vitamins include, but are not limited to, vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin. Suitable forms of any of the above include salts of vitamins, derivatives of vitamins, compounds having the same or similar activity as vitamins, and metabolites of vitamins.

[0121] In some embodiments, the pharmaceutical composition comprises an additive. Non-limiting examples of suitable additives include buffering agents, preservatives, stabilizers, binders, compression agents, lubricants, dispersion enhancers, disintegrants, flavors, sweeteners, and colorants.

[0122] In some embodiments, the additive is a buffering agent. Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.

[0123] In some embodiments, the additive comprises a preservative. Non-limiting examples of suitable preservatives include antioxidants (e.g., α-tocopherol and ascorbate) and antimicrobial agents (e.g., parabens, chlorobutanol, and phenol).

[0124] In some embodiments, the pharmaceutical composition comprises a binder as an excipient. Non-limiting examples of suitable binders include starch, pregelatinized starch, gelatin, polyvinylpyrrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamide, polyvinyloxoazolidone, polyvinyl alcohol, C 12 ~C 18 Included are fatty acid alcohols, polyethylene glycols, polyols, sugars, oligosaccharides, and combinations thereof.

[0125] In some embodiments, the pharmaceutical composition comprises a lubricant as an excipient. Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oil, sterotex, polyoxyethylene monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

[0126] In some embodiments, the pharmaceutical composition comprises a dispersion enhancer as an excipient. Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidone, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as a high HLB emulsifier surfactant.

[0127] In some embodiments, the pharmaceutical composition comprises a disintegrant as an additive. In some embodiments, the disintegrant is a non-effervescent disintegrant. Non-limiting examples of suitable non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized starches and modified starches, sweeteners, clays such as bentonite, microcrystalline cellulose, alginates, sodium starch glycolate, gums such as agar, gaur, carob, karaya, pectin, and tragacanth. In some embodiments, the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid and sodium bicarbonate in combination with tartaric acid.

[0128] In some embodiments, the pharmaceutical composition is a food (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, the elderly, or other special groups, a functional food, beverage, a food or beverage for a specific health use, a dietary supplement, a food or beverage for a patient, or an animal feed. Specific examples of foods and beverages include: various beverages, such as juices, soft drinks, tea drinks, beverage preparations, jelly drinks, and functional drinks; alcoholic beverages, such as beer; carbohydrate-containing foods, such as rice foods, noodles, bread, and pasta; paste products, such as fish ham, sausage, and seafood paste products; retort pouch products, such as curry, foods with thick sauces, and Chinese soup; soup; dairy products, such as milk, dairy drinks, ice cream, cheese, and yogurt; fermented products, such as fermented miso, yogurt, fermented drinks, and pickles; soy products; various confectionery products, such as biscuits, cookies, and the like, candy, chewing gum, gummy candies, cold desserts, such as jelly, cream caramel, and frozen desserts; instant foods, such as instant soups and instant soybean soups; microwavable foods; and the like. Further examples include health foods and health drinks prepared in the form of powders, granules, tablets, capsules, liquids, pastes, and jellies.

[0129] In some embodiments, the pharmaceutical composition is a food product for animals, including humans. Non-human animals are not particularly limited, and the composition may be used for a variety of livestock, poultry, pets, laboratory animals, and the like. Specific examples of such animals include, but are not limited to, pigs, cows, horses, sheep, goats, chickens, wild ducks, ostriches, ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, and the like.

[0130] Dosage form As used herein, for example, T HAlso provided is a dosage form comprising Prevotella bacteria for use in a method for treating or preventing a rhesus malabsorption mediated condition (e.g., atopic dermatitis and / or food allergies). A pharmaceutical composition comprising Prevotella bacteria may be formulated, for example, as a solid dosage form for oral administration. The solid dosage form may include one or more additives (e.g., pharmaceutically acceptable additives). The Prevotella bacteria in the solid dosage form may be isolated Prevotella bacteria. Optionally, the Prevotella bacteria in the solid dosage form may be lyophilized. Optionally, the Prevotella bacteria in the solid dosage form are live. Optionally, the Prevotella bacteria in the solid dosage form are gamma irradiated. The solid dosage form may include a tablet, mini-tablet, capsule, pill, or powder; or a combination of these forms (e.g., mini-tablets in a capsule).

[0131] In certain embodiments, the pharmaceutical compositions provided herein are prepared as solid dosage forms comprising Prevotella bacteria and a pharmaceutically acceptable carrier.

[0132] In some embodiments, the solid dosage form comprises a capsule. The capsule may include an enteric coating. The capsule may be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. The capsule may include Prevotella bacteria powder (e.g., freeze-dried Prevotella bacteria).

[0133] In some embodiments, the solid dosage forms described herein can be, for example, tablets or mini-tablets. In some embodiments, multiple mini-tablets can be present in (e.g., filled into) a capsule.

[0134] In some embodiments, the solid dosage form comprises a tablet (greater than 4 mm) (e.g., 5 mm to 17 mm). For example, the tablet is a 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, or 17 mm tablet. This size refers to the diameter of the tablet, as known in the art. As used herein, tablet size refers to the size of the tablet before application of an enteric coating.

[0135] In some embodiments, the solid dosage form comprises mini-tablets. The mini-tablets can range in size from 1 mm to 4 mm, for example, the mini-tablets can be 1 mm mini-tablets, 1.5 mm mini-tablets, 2 mm mini-tablets, 3 mm mini-tablets, or 4 mm mini-tablets. This size refers to the diameter of the mini-tablets, as known in the art. As used herein, the size of the mini-tablets refers to the size of the mini-tablets before application of an enteric coating.

[0136] The mini-tablets may be present in a capsule. The capsule may be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. The capsule containing the mini-tablets may include a single layer coating, such as a non-enteric coating such as HPMC (hydroxypropyl methylcellulose) or gelatin. The mini-tablets may be present in a capsule; the number of mini-tablets in a capsule will depend on the size of the capsule and the size of the mini-tablets. As an example, a size 0 capsule may contain 31-35 mini-tablets (average 33) that are 3 mm mini-tablets.

[0137] The solid dosage forms described herein (e.g., tablets or minitablets) may be enterically coated.

[0138] Solid dosage forms may include coatings. Solid dosage forms may include a single layer of coating, such as an enteric coating, e.g., a Eudragit-based coating, e.g., EUDRAGIT L30 D-55, triethyl citrate, and talc. Solid dosage forms may include two layers of coating. For example, an inner coating may include, e.g., EUDRAGIT L30 D-55, triethyl citrate, talc, citric acid anhydride, and sodium hydroxide, while an outer coating may include, e.g., EUDRAGIT L30 D-55, triethyl citrate, and talc. EUDRAGIT is a brand name for various polymethacrylic acid-based copolymers. EUDRAGIT includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic / acrylic acid esters, or their derivatives. Eudragit is an amorphous polymer with a glass transition temperature of 9 to over 150°C. Eudragits are non-biodegradable, non-absorbable, and non-toxic. Anionic Eudragit L dissolves at pH > 6 and is used for enteric coatings, while Eudragit S, soluble at pH > 7, is used for colonic targeting. Eudragit RL and RS, which contain quaternary ammonium groups, are water-insoluble but swellable / water-permeable polymers that are suitable for sustained-release fill coating applications. Cationic Eudragit E, insoluble at pH > 5, can prevent drug release in saliva.

[0139] Solid dosage forms (eg, capsules) may comprise a single layer coating, for example, a non-enteric coating such as HPMC (hydroxylpropylmethylcellulose) or gelatin.

[0140] Pharmaceutical compositions containing Prevotella bacteria can be formulated, for example, as suspensions for oral administration or injection. Injectable administration includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. In the case of a suspension, the Prevotella bacteria can be present in a buffer, such as a pharmaceutically acceptable buffer (e.g., saline or PBS). The suspension can include one or more additives (e.g., pharmaceutically acceptable additives). The suspension can include, for example, sucrose or glucose. The Prevotella bacteria in the suspension can be isolated Prevotella bacteria. Optionally, the Prevotella bacteria in the suspension dosage form can be lyophilized. Optionally, the Prevotella bacteria in the solid dosage form are viable. Optionally, the Prevotella bacteria in the suspension can be gamma-irradiated.

[0141] Dosage For oral administration to human subjects, the dose of Prevotella bacteria is, for example, about 2 x 10 6 ~about 2×10 16 This dose can be, for example, about 1 x 10 particles. 7 ~Approx. 1×10 15 pieces, about 1×10 8 ~Approx. 1×10 14 pieces, about 1×10 9 ~Approx. 1×10 13 pieces, about 1×10 10 ~Approx. 1×10 14 pieces, or approximately 1 x 10 8 ~Approx. 1×10 12 This dose can be, for example, about 2 x 10 particles. 6 pieces, approximately 2×10 7 pieces, approximately 2×10 8 pieces, approximately 2×10 9 pieces, about 1×10 10 pieces, approximately 2×10 10 pieces, approximately 2×10 11 pieces, approximately 2×10 12 pieces, approximately 2×10 13 pieces, approximately 2×1014 pieces, or approximately 1 x 10 15 This dose can be, for example, about 2 x 10 particles. 14 This dose can be, for example, about 2 x 10 particles. 12 The particles may be, for example, about 2×10 10 The particles may be, for example, about 1×10 10 The number of particles can be determined, for example, by NTA.

[0142] For oral administration to human subjects, the dose of Prevotella bacteria can be based on, for example, total protein. This dose can be, for example, about 5 mg to about 900 mg of total protein. This dose can be, for example, about 20 mg to about 800 mg, about 50 mg to about 700 mg, about 75 mg to about 600 mg, about 100 mg to about 500 mg, about 250 mg to about 750 mg, or about 200 mg to about 500 mg of total protein. This dose can be, for example, about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, or about 750 mg of total protein. This dose can be, for example, about 10 mg of total protein. Total protein can be determined, for example, by Bradford assay or BCA assay.

[0143] For administration by injection (e.g., intravenous administration) to a human subject, the dose of Prevotella bacteria may be, for example, about 1 x 10 6 ~Approx. 1×10 16 This dose can be, for example, about 1 x 10 particles. 7 ~Approx. 1×10 15 pieces, about 1×10 8 ~Approx. 1×10 14 pieces, about 1×10 9 ~Approx. 1×10 13 pieces, about 1×10 10 ~Approx. 1×10 14 pieces, or approximately 1 x 10 8 ~Approx. 1×10 12 This dose can be, for example, about 2 x 10 particles.6 pieces, approximately 2×10 7 pieces, approximately 2×10 8 pieces, approximately 2×10 9 pieces, about 1×10 10 pieces, approximately 2×10 10 pieces, approximately 2×10 11 pieces, approximately 2×10 12 pieces, approximately 2×10 13 pieces, approximately 2×10 14 pieces, or approximately 1 x 10 15 This dose can be, for example, about 1 x 10 particles. 15 This dose can be, for example, about 2 x 10 particles. 14 This dose can be, for example, 2 x 10 particles. 13 The number of particles can be determined, for example, by NTA.

[0144] When administered by injection (e.g., intravenously), the dose of Prevotella bacteria can be, for example, about 5 mg to about 900 mg of total protein. This dose can be, for example, about 20 mg to about 800 mg, about 50 mg to about 700 mg, about 75 mg to about 600 mg, about 100 mg to about 500 mg, about 250 mg to about 750 mg, or about 200 mg to about 500 mg of total protein. This dose can be, for example, 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, or about 750 mg of total protein. This dose can be, for example, about 700 mg of total protein. This dose can be, for example, about 350 mg of total protein. This dose can be, for example, about 175 mg of total protein. Total protein can be determined, for example, by Bradford assay or BCA assay.

[0145] In certain embodiments, the pharmaceutical composition (e.g., a total dose of the composition administered, e.g., once or twice daily) contains at least 1 x 10 10 Total cells (e.g., at least 1 x 10 10 Total cells, at least 2 x 10 10 Total cells, at least 3 x 1010 Total cells, at least 4 x 10 10 Total cells, at least 5 x 10 10 Total cells, at least 6 x 10 10 Total cells, at least 7 x 10 10 Total cells, at least 8 x 10 10 Total cells, at least 9 x 10 10 Total cells, at least 1 x 10 11 In some embodiments, the pharmaceutical composition comprises 9 x 10 total cells of Prevotella bacteria. 11 0.01 or less total cells (e.g., 1 x 10 10 Total cells, 2 x 10 or less 10 Total cells less than 3 x 10 10 Total cells, 4 x 10 or less 10 Total cells, 5 x 10 or less 10 Total cells, 6 x 10 or less 10 Total cells, 7 x 10 or less 10 Total cells, 8 x 10 or less 10 Total cells, 9 x 10 or less 10 Total cells less than 1 x 10 11 Total cells, 2 x 10 or less 11 Total cells less than 3 x 10 11 Total cells, 4 x 10 or less 11 Total cells, 5 x 10 or less 11 Total cells, 6 x 10 or less 11 Total cells, 7 x 10 or less 11 Total cells, 8 x 10 or less 11 In some embodiments, the pharmaceutical composition comprises about 6 x 10 Prevotella bacteria. 9 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 10 In some embodiments, the pharmaceutical composition comprises about 8 x 10 total cells of Prevotella bacteria. 10 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 11In some embodiments, the pharmaceutical composition comprises about 3.2 x 10 total cells of Prevotella bacteria. 11 In some embodiments, the pharmaceutical composition comprises about 8 x 10 total cells of Prevotella bacteria. 11 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 10 pieces~approx. 8×10 11 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 10 ~Approx. 1.6×10 11 In some embodiments, the pharmaceutical composition comprises about 8 x 10 total cells of Prevotella bacteria. 10 ~Approx. 8×10 11 In some embodiments, the pharmaceutical composition comprises about 1.6 x 10 total cells of Prevotella bacteria. 11 pieces~approx. 8×10 11 Contains a total of 100 cells of Prevotella bacteria.

[0146] In certain embodiments, provided herein are solid dosage forms comprising Prevotella bacteria. In some embodiments, the solid dosage forms comprise an enteric coating. In some embodiments, the solid dosage forms are capsules, e.g., enteric-coated capsules. In some embodiments, each capsule contains about 8 x 10 10 In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered to a subject, e.g., once or twice daily. In some embodiments, 1 capsule (e.g., about 8 x 10 10 In some embodiments, two capsules (e.g., each containing about 8 x 10 total cells) are administered to a subject, e.g., once or twice daily. 10In some embodiments, four capsules (e.g., each containing about 8 x 10 total cells) are administered to a subject, e.g., once or twice daily. 10 In some embodiments, 10 capsules (e.g., each containing about 8 x 10 total cells) are administered to a subject, e.g., once or twice daily. 10 The capsules (containing 100 total cells) are administered to a subject, for example, once or twice daily. In some embodiments, the Prevotella bacteria in the capsules are freeze-dried (e.g., into a powder).

[0147] In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated tablet. In some embodiments, the capsule contains about 8 x 10 10 In some embodiments, the capsule contains about 1.6 x 10 total cells of Prevotella bacteria (e.g., a total dose of one capsule or multiple capsules). 11 In some embodiments, the capsule contains about 3.2 x 10 total cells of Prevotella bacteria (e.g., a total dose of one capsule or multiple capsules). 11 In some embodiments, the capsule contains about 8 x 10 total cells of Prevotella bacteria (e.g., a total dose of one capsule or multiple capsules). 11 In some embodiments, the Prevotella bacteria in the capsules are lyophilized (e.g., into a powder).

[0148] 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 has a diameter of 5 mm to 17 mm. In some embodiments, the tablet has a diameter of about 8 x 10 10In some embodiments, the tablet contains about 1.6 x 10 total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). 11 In some embodiments, the tablet contains about 3.2 x 10 total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). 11 In some embodiments, the tablet contains about 8 x 10 total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). 11 In some embodiments, the Prevotella bacteria in the tablet comprises 0.05% total cells of Prevotella bacteria (e.g., a total dose of one tablet or multiple tablets). In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[0149] In some embodiments, the solid dosage form comprises mini-tablets. In some embodiments, the mini-tablets are enteric coated. In some embodiments, the mini-tablets are 1 mm to 4 mm in diameter. In some embodiments, the mini-tablets (e.g., enteric coated mini-tablets) are 1 mm mini-tablets, 1.5 mm mini-tablets, 2 mm mini-tablets, 3 mm mini-tablets, or 4 mm mini-tablets. In some embodiments, the solid dosage form is about 8 x 10 10 In some embodiments, the solid dosage form comprises a mini-tablet containing about 1.6 x 10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). 11 In some embodiments, the solid dosage form comprises a mini-tablet containing about 3.2 x 10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). 11 In some embodiments, the solid dosage form comprises a mini-tablet containing about 8 x 10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). 11In some embodiments, the mini-tablets comprise mini-tablets containing about 8×10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). In some embodiments, the Prevotella bacteria in the mini-tablets are freeze-dried. In some embodiments, the mini-tablets (e.g., enteric-coated mini-tablets) are contained in a capsule. In some embodiments, the capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule comprises (e.g., is coated with) a non-enteric coating (e.g., HPMC (hydroxylpropylmethylcellulose) or gelatin). In some embodiments, the capsule comprises a non-enteric coating. In some embodiments, the capsule comprises hydroxylpropylmethylcellulose (HPMC). In some embodiments, the capsule comprises gelatin. In some embodiments, the mini-tablets comprise about 8×10 total cells of Prevotella bacteria (e.g., a total dose of a plurality of mini-tablets). ... 11 Mini-tablets (e.g., enteric-coated mini-tablets) containing 100 whole cells of Prevotella bacteria are contained in a capsule, and optionally, the capsule contains HPMC.

[0150] Gamma irradiation Powder (eg, powder of Prevotella bacteria) can be gamma irradiated at ambient temperature with 17.5 kGy radiation units.

[0151] Frozen biomass (eg, biomass of Prevotella bacteria) can be irradiated with gamma rays at 25 kGy radiation units in the presence of dry ice.

[0152] T H 2-mediated conditions T that can be treated and / or prevented by Prevotella bacteria (e.g., pharmaceutical compositions thereof) HType 2 (type 2)-mediated conditions include conditions associated with elevated levels (e.g., mRNA or protein levels) of interleukin (IL)-4, IL-5, IL-13, IL-19, IL-21, IL-31, IL-33, and / or TSLP (thymic stromal lymphopoietin), e.g., during the development or course of the disease.

[0153] The Prevotella bacteria (e.g., a pharmaceutical composition thereof) can reduce levels (e.g., mRNA levels or protein levels) of interleukin (IL)-4, IL-5, IL-13, IL-19, IL-21, IL-31, IL-33, and / or TSLP (thymic stromal lymphopoietin), e.g., the Prevotella bacteria (e.g., a pharmaceutical composition thereof) cause a reduction compared to levels in the absence (or before) of administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof). The pharmaceutical composition can reduce these levels by, for example, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%.

[0154] T that can be treated and / or prevented by Prevotella bacteria (e.g., pharmaceutical compositions thereof) H Type 2 (type 2)-mediated conditions include conditions associated with elevated levels (eg, mRNA or protein levels) of IgG1, IgE, and / or IgA, eg, during the development or course of the disease.

[0155] The Prevotella bacteria (e.g., a pharmaceutical composition thereof) can reduce levels (e.g., mRNA levels or protein levels) of IgG1, IgE, and / or IgA, e.g., the Prevotella bacteria (e.g., a pharmaceutical composition thereof) causes a reduction compared to levels in the absence (or before) of administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof). The pharmaceutical composition can reduce these levels by, for example, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%.

[0156] T H The two-mediated condition may include asthma, atopic dermatitis, eosinophilic disease, or allergy (e.g., seasonal allergy, pet allergy, or food allergy). The allergy may include food allergy, seasonal allergic rhinitis, or pet allergy. The food allergy may include peanut allergy. The food allergy may include milk allergy, hen's egg allergy, fish allergy, crustacean shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. The food allergy may include allergy to a food antigen. The food antigen may include peanut antigen. The food allergy may include allergy to a food antigen, and the food antigen may include milk antigen, hen's egg antigen, fish antigen, shellfish antigen, tree nut antigen, wheat antigen, or soy antigen.

[0157] Specific T H Some of the two-mediated conditions are described in further detail below.

[0158] Allergic rhinitis In some embodiments, T HTwo-mediated conditions include allergic rhinitis (i.e., hay fever). Allergic rhinitis occurs when allergens cause inflammation in the nose. Potential allergen types include pollen, pet hair, dander, house dust mites, mold, smoke, and perfumes, individually or in combination. Symptoms of allergic rhinitis may include, individually or in combination, a runny or stuffy nose; itchy eyes, mouth, throat, or skin; sneezing; coughing; and fatigue.

[0159] asthma In some embodiments, T H Two-mediated conditions include asthma (e.g., allergic asthma). Asthma occurs when the airways in the lungs become inflamed, for example. One type of asthma included in the conditions relevant to the disclosure herein is atopic asthma. Symptoms of asthma may include coughing, wheezing, shortness of breath, and chest tightness, either individually or in combination.

[0160] Atopic dermatitis In some embodiments, T H Two-mediated conditions include atopic dermatitis (i.e., eczema). Atopic dermatitis occurs when the skin becomes inflamed. Atopic dermatitis may be accompanied by allergic rhinitis and / or asthma. Symptoms of atopic dermatitis may include dry skin, redness, itchiness, rash, and sores, either individually or in combination.

[0161] hives In some embodiments, T H Two-mediated conditions include urticaria (i.e., hives). Urticaria occurs when the skin develops swollen, red welts. The condition can be caused by leakage of plasma from blood vessels due to histamine, for example, as a result of an allergic reaction. Symptoms of urticaria can include a cluster of welts, itching, and swelling, either individually or in combination.

[0162] angioedema In some embodiments, TH Two-mediated conditions include angioedema (i.e., deep tissue swelling). When this swelling is under the skin, conditions similar to urticaria in other respects can be classified as angioedema. This condition can be caused by leakage of plasma from blood vessels due to histamine, for example, as a result of an allergic reaction. Symptoms of angioedema can include, individually or in combination, swelling of the eyes, mouth, hands, feet, or throat; difficulty breathing; and stomach cramps.

[0163] food allergies In some embodiments, T H Two-mediated conditions include food allergies. Food allergies occur when a food (e.g., its allergen) triggers an abnormal immune response. Typical types of foods that can trigger a reaction include eggs, milk, peanuts, tree nuts (e.g., walnuts), fish, shellfish, wheat, and soybeans. In addition, seeds (e.g., sesame, mustard), fruits, and rice can also cause food allergies. Symptoms can include, individually or in combination, itching in the mouth; hives; swelling in parts of the body such as the face; difficulty breathing; abdominal discomfort; and dizziness.

[0164] Insect-induced allergies In some embodiments, T H

[0003] 2-mediated conditions include insect-induced allergies, which occur when the immune system reacts to insect stings or bites. Typical types of insects that can cause such reactions include wasps, bees, hornets, yellow-jackets, ants, mosquitoes, bedbugs, fleas, and ticks.

[0165] Drug allergies In some embodiments, T HTwo-mediated conditions include drug allergies. Drug allergies occur as adverse reactions when exposed to drugs. Some types of drugs that can cause such reactions include penicillin, sulfonamides, anticonvulsants, aspirin, and chemotherapy drugs. Symptoms of drug allergies may include fever, itching, hives, rash, swelling, and shortness of breath, either individually or in combination.

[0166] anaphylaxis In some embodiments, T H Two-mediated conditions include anaphylaxis, which occurs when there is a severe reaction to food, insect venom, or a drug. Anaphylaxis can affect the entire body and can alter breathing, blood pressure, and heart rate.

[0167] Eosinophilia In some embodiments, T H 2-mediated conditions include eosinophilia (e.g., primary eosinophilia), which occurs when the number of eosinophils exceeds a certain threshold in a specific site or in the peripheral blood.

[0168] These T H For each of the T 2 -mediated conditions, the specific T 2 -mediated conditions that are treated by the methods described herein for treating or preventing such conditions are H The administration of steroids may result in the reduction, stabilization, or otherwise amelioration of symptoms of a steroid-2-mediated condition, including those described herein.

[0169] Additional medications In certain aspects, the methods provided herein involve administering a therapeutic agent, alone or in combination with another therapeutic agent (e.g., T HThis includes administering to a subject the bacteria and / or bacterial compositions described herein (e.g., a pharmaceutical composition containing Prevotella bacteria) in combination with another therapeutic agent for treating or preventing a rhesus malabsorption-mediated condition (e.g., atopic dermatitis and / or food allergies). The pharmaceutical composition containing Prevotella bacteria may be administered in combination with, for example, an anti-inflammatory agent. The anti-inflammatory agent may be an antihistamine (e.g., cetirizine, fexofenadine, or diphenhydramine), epinephrine, a corticosteroid (oral or topical) (e.g., betamethasone valerate, hydrocortisone, or prednisone), a calcineurin inhibitor (e.g., tacrolimus or pimecrolimus), cyclosporine, interferon gamma-1b, or dupilumab. Topical corticosteroids that may be used include alclometasone propionate, betamethasone propionate, betamethasone valerate, clobetasol propionate, desonide, desoximetasone, fluocinolone acetonide, fluocinonide, fluticasone propionate, halobetasol propionate, hydrocortisone, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, triamcinolone acetonide, and triamcinolone acetate.

[0170] In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the other treatment may be administered to the subject in any order. In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the other treatment are administered together.

[0171] In some embodiments, the Prevotella bacteria-containing pharmaceutical composition is administered to the subject prior to (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, 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) administration of the additional therapeutic agent. In some embodiments, the Prevotella bacteria-containing pharmaceutical composition is administered to the subject after administration of the additional therapeutic agent (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, 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). In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the additional therapeutic agent are administered to the subject simultaneously or nearly simultaneously (e.g., within one hour of each other). In some embodiments, the subject is administered an antibiotic prior to (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, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days prior to) administering the Prevotella bacteria-containing pharmaceutical composition to the subject.In some embodiments, an antibiotic is administered to a subject after (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) administering a Prevotella bacteria-containing pharmaceutical composition to the subject. In some embodiments, the Prevotella bacteria-containing pharmaceutical composition and the antibiotic are administered to the subject simultaneously or nearly simultaneously (e.g., within one hour of each other).

[0172] In certain embodiments, the subject may be undergoing surgery, including but not limited to, preventative surgery, diagnostic or staging surgery, curative surgery, and palliative surgery.

[0173] In some embodiments, the additional therapeutic agent is an antibiotic. "Antibiotic" broadly refers to a compound that can inhibit or prevent bacterial infection. Antibiotics can be classified in various ways (e.g., use for specific infections, mechanism of action, bioavailability, spectrum of target microorganisms (e.g., gram-negative vs. gram-positive, aerobic vs. anaerobic)), and can be used to kill specific bacteria in specific areas ("niches") of the host (Leekha, et al. 2011. General Principles of Antimicrobial Therapy. Mayo Clin Proc. 86(2):156-167). In certain embodiments, antibiotics can be used to selectively target bacteria in specific niches. In some embodiments, antibiotics are administered after bacterial treatment. In some embodiments, antibiotics are administered after bacterial treatment to eliminate engraftment.

[0174] In some aspects, antibiotics may be selected based on their bactericidal or bacteriostatic properties. Bactericidal antibiotics include those with a mechanism of action that disrupts cell walls (e.g., β-lactams), cell membranes (e.g., daptomycin), or bacterial DNA (e.g., fluoroquinolones). Bacteriostatic agents inhibit bacterial replication and include sulfonamides, tetracyclines, and macrolides, which act by inhibiting protein synthesis. Furthermore, while some agents may be bactericidal in certain organisms and bacteriostatic in others, knowing the target organism allows one of skill in the art to select antibiotics with appropriate properties. In certain treatment conditions, bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics. Therefore, in certain embodiments, bactericidal and bacteriostatic antibiotics are not used in combination.

[0175] Antibiotics include, but are not limited to, aminoglycosides, ansamycins, carbacephems, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, oxazolidonones, penicillins, polypeptide antibiotics, quinolones, fluoroquinolones, sulfonamides, tetracyclines, and antimycobacterial compounds, and combinations thereof.

[0176] Aminoglycosides include, but are not limited to, amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, and spectinomycin. Aminoglycosides are effective against, for example, Gram-negative bacteria (e.g., Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis) and certain aerobic bacteria, but are less effective against obligate / facultative anaerobes. Aminoglycosides are thought to bind to the bacterial 30S or 50S ribosomal subunits, thereby inhibiting bacterial protein synthesis.

[0177] Ansamycins include, but are not limited to, geldanamycin, herbimycin, rifamycin, and streptovaricin. Geldanamycin and herbimycin are believed to inhibit or alter the function of heat shock protein 90.

[0178] Carbacephems include, but are not limited to, loracarbef. Carbacephems are believed to inhibit bacterial cell wall synthesis.

[0179] Carbapenems include, but are not limited to, ertapenem, doripenem, imipenem / cilastatin, and meropenem. As broad-spectrum antibiotics, carbapenems are bactericidal against both gram-positive and gram-negative bacteria. Carbapenems are believed to inhibit bacterial cell wall synthesis.

[0180] Cephalosporins include, but are not limited to, cefadroxil, cefazolin, cefalotin, cefalothin, cephalexin, cefaclor, cefamandole, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, ceftaroline fosamil, and ceftobiprole. Certain cephalosporins are effective against, for example, gram-negative and gram-positive bacteria (e.g., Pseudomonas), and certain cephalosporins are effective against methicillin-resistant Staphylococcus aureus (MRSA). Cephalosporins are believed to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

[0181] Glycopeptides include, but are not limited to, teicoplanin, vancomycin, and telavancin. Glycopeptides are effective against aerobic and anaerobic Gram-positive bacteria (e.g., MRSA and Clostridium difficile). Glycopeptides are thought to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

[0182] Lincosamides include, but are not limited to, clindamycin and lincomycin. Lincosamides are effective against, for example, anaerobic bacteria, as well as Staphylococcus and Streptococcus. Lincosamides are believed to bind to the 50S ribosomal subunit of bacteria, thereby inhibiting bacterial protein synthesis.

[0183] Lipopeptides include, but are not limited to, daptomycin. Lipopeptides are effective against, for example, Gram-positive bacteria. Lipopeptides are thought to bind to bacterial membranes and cause rapid depolarization.

[0184] Macrolides include, but are not limited to, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, and spiramycin. Macrolides are effective against, for example, Streptococcus and Mycoplasma. Macrolides are thought to bind to the bacterial 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

[0185] Monobactams include, but are not limited to, aztreonam. Monobactams are effective against, for example, Gram-negative bacteria. Monobactams are believed to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

[0186] Nitrofurans include, but are not limited to, furazolidone and nitrofurantoin.

[0187] Oxazolidnones include, but are not limited to, Linezolid, Posizolid, Radezolid, and Torezolid. Oxazolidnones are believed to be protein synthesis inhibitors.

[0188] Penicillins include, but are not limited to, amoxicillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, temocillin, and ticarcillin. Penicillins are effective against, for example, gram-positive bacteria and facultative anaerobes, such as Streptococcus, Borrelia, and Treponema. Penicillins are thought to inhibit bacterial cell wall synthesis by disrupting the synthesis of the peptidoglycan layer of the bacterial cell wall.

[0189] Penicillin combinations include, but are not limited to: amoxicillin / clavulanic acid, ampicillin / sulbactam, piperacillin / tazobactam, and ticarcillin / clavulanic acid.

[0190] Polypeptide antibiotics include, but are not limited to, bacitracin, colistin, and polymyxins B and E. Polypeptide antibiotics are effective against, for example, Gram-negative bacteria. Certain polypeptide antibiotics inhibit isoprenyl pyrophosphate, which is involved in the synthesis of the peptidoglycan layer of the bacterial cell wall, while others are thought to destabilize the bacterial outer membrane by displacing bacterial counterions.

[0191] Quinolones and fluoroquinolones include, but are not limited to, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin, grepafloxacin, sparfloxacin, and temafloxacin. Quinolones / fluoroquinolones are effective against, for example, Streptococcus and Neisseria. Quinolones / fluoroquinolones are thought to inhibit bacterial DNA gyrase or topoisomerase IV, thereby inhibiting DNA replication and transcription.

[0192] Sulfonamides include, but are not limited to, mafenide, sulfacetamide, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfanilimide, sulfasalazine, sulfisoxazole, trimethoprim-sulfamethoxazole (cotrimoxazole), and sulfonamide chrysoidine. Sulfonamides are believed to inhibit folate synthesis by competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.

[0193] Tetracyclines include, but are not limited to, demeclocycline, doxycycline, minocycline, oxytetracycline, and tetracycline. Tetracyclines are effective against, for example, Gram-negative bacteria. Tetracyclines are thought to bind to the bacterial 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

[0194] Antimycobacterial compounds include, but are not limited to: clofazimine, dapsone, capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide, rifampicin, rifabutin, rifapentine, and streptomycin.

[0195] Suitable antibiotics also include arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin / dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin / clavulanic acid, ampicillin / sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin P1, clarithromycin, erythromycin, furazolidone, fusidic acid, sodium fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazole, mikamycin, mutacin B-Ny266, mutacin B-JH1 140, mutacin J-T8, nisin, nisin A, novobiocin, oleandomycin, ostreoglycin, piperacillin / tazobactam, pristinamycin, ramoplanin, ranalexin, reuterin, rifaximin, rosamicin, rosaramycin, spectinomycin, spiramycin, stafilomycin, streptogramin, streptogramin A, synergistin, taurolidine, teicoplanin, telithromycin, ticarcillin / clavulanic acid, triacetyloleandomycin, tylosin, tyrocidine, tyrothricin, vancomycin, vemamycin, and virginiamycin.

[0196] In some embodiments, the additional therapeutic agent comprises administering to the subject a therapeutic bacterium (e.g., Prevotella bacteria) and / or a therapeutic combination of bacteria such that a healthy microbiome can be re-established in the subject. In some embodiments, the therapeutic bacterium is a probiotic bacterium.

[0197] Some of the specific additional therapeutic agents are described in further detail below.

[0198] Allergic rhinitis In some embodiments, T HThe two-mediated condition includes allergic rhinitis, and the additional therapeutic agent includes drugs that can be used to treat allergic rhinitis. Such drugs include, individually or in combination, corticosteroids (e.g., prednisone, methylprednisolone, triamcinolone acetonide, betamethasone), antihistamines (e.g., acrivastine, alimemazine, antazoline, astemizole, azelastine, bepotastine, bilastine, bromazine, brompheniramine, carbinoxamine, cetirizine, chlorcyclizine, chloropyramine, chlorphenamine), and the like. , clemastine, cyclizine, cyproheptadine, desloratadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimethindene, diphenhydramine, doxylamine, ebastine, fexofenadine, hydroxyzine, ketotifen, levocabastine, levocetirizine, loratadine, meclizine, mepyramine, mizolastine, olopatadine, orphenadrine, pheniramine, promethazine, quifenadine, levometin ... Patadine, terfenadine, tripelennamine, triprolidine), mast cell stabilizers (e.g., cromolyn), decongestants (e.g., beclomethasone, budesonide, ciclesonide, dexamethasone, ephedrine, flunisolide, fluticasone, fluticasone furoate, fluticasone propionate, levomethamphetamine, mometasone, naphazoline, oxymetazoline, phenylephrine, phenylpropanolamine, prednisolone These include benzodiazepines, propylhexedrine, pseudoephedrine, synephrine, tetrizoline, tixocortol, tramazoline, triamcinolone, triamcinolone acetonide, xylometazoline), leukotriene receptor antagonists (e.g., montelukast, zafirlukast, zileuton, MK-886, meclofenamate sodium), and immunotherapeutics (e.g., immunotherapeutics containing a form of the allergen itself, or an immunotherapeutic containing a form of an antibody such as omalizumab). These drugs are also commonly used for other types of allergies, whether they occur as a single type of allergy or in combination with other types of allergies.

[0199] asthma In some embodiments, T H The two-mediated conditions include asthma (e.g., allergic asthma), and the additional therapeutic agents include agents that can be used to treat asthma, including, individually or in combination, corticosteroids, decongestants (some of which are also corticosteroids), mast cell stabilizers, leukotriene modifiers, and immunotherapeutics provided herein for the treatment of allergic rhinitis. Additionally, for asthma, the medications also include, individually or in combination, beta agonists (e.g., salmeterol, formoterol, albuterol, levalbuterol), certain corticosterone and beta agonist combinations (e.g., fluticasone-salmeterol, budesonide-formoterol, budesonide-formoterol, formoterol-mometasone), additional immunotherapeutic agents (e.g., mepolizumab, dupilumab, reslizumab, and benralizumab), and certain other drugs (e.g., theofelline, ipratropium). These medications can be provided by use of an inhaler, as an injection (e.g., an injection for antibody forms), or as a pill (e.g., a sublingual tablet for allergen immunotherapy).

[0200] Atopic dermatitis In some embodiments, T H The two-mediated condition includes atopic dermatitis, and the additional therapeutic agent includes a drug that can be used to treat atopic dermatitis. Such drugs include corticosteroids (e.g., prednisone) and immunotherapeutic agents (e.g., dupilumab), individually or in combination, provided herein for the treatment of allergic rhinitis or asthma. In addition, for atopic dermatitis, the drugs also include calcineurin inhibitors (e.g., tacrolimus, pimecrolimus), certain nutritional supplements (e.g., vitamin D), immunosuppressants (e.g., cyclosporine, methotrexate, interferon gamma-1b, mycophenolate mofetil, azathioprine), and other drugs (e.g., crisaborole).

[0201] hives In some embodiments, T H The biphasic condition includes urticaria, and the additional therapeutic agent includes a drug that can be used to treat urticaria. Such drugs include, individually or in combination, antihistamines (e.g., diphenhydramine, loratadine, fexofenadine, cetirizine, desloratadine), corticosteroids (e.g., prednisone), leukotriene receptor antagonists, and immunotherapeutic agents (e.g., omalizumab) provided herein for the treatment of allergic rhinitis or asthma. In addition, for urticaria, the drug may also include other antihistamines (e.g., ranitidine, cimetidine, famotidine), immunosuppressants (e.g., cyclosporine, tacrolimus, sirolimus, mycophenolic acid), anti-inflammatory drugs (e.g., dapsone, sulfasalazine, hydroxychloroquine), corticosteroids (e.g., cortisone), and hormones (e.g., epinephrine).

[0202] angioedema In some embodiments, T H The biphasic condition includes angioedema, and the additional therapeutic agent includes drugs that can be used to treat angioedema. Such drugs include, individually or in combination, antihistamines (e.g., diphenhydramine, loratadine, fexofenadine, cetirizine, desloratadine), corticosteroids (e.g., prednisone), leukotriene receptor antagonists, and immunotherapeutic agents (e.g., omalizumab) provided herein for the treatment of allergic rhinitis or asthma. In addition, for angioedema, the drug may also include other antihistamines (e.g., ranitidine, cimetidine, famotidine), immunosuppressants (e.g., cyclosporine, tacrolimus, sirolimus, mycophenolic acid), anti-inflammatory drugs (e.g., dapsone, sulfasalazine, hydroxychloroquine), corticosteroids (e.g., cortisone), and hormones (e.g., epinephrine).

[0203] food allergies In some embodiments, T HThe two-mediated condition includes food allergy, and the additional therapeutic agent includes drugs that can be used to treat food allergy, such as epinephrine, antihistamines, glucocorticoid steroids, and immunotherapeutics (e.g., immunotherapeutics that include forms of the allergen itself, or antibody forms such as omalizumab), either individually or in combination.

[0204] Insect-induced allergies In some embodiments, T H The two-mediated condition includes insect-induced allergies, and the additional therapeutic agents include drugs that can be used to treat insect-induced allergies, such as antihistamines.

[0205] Drug allergies In some embodiments, T H Two-mediated conditions include drug allergies, and additional therapeutic agents include drugs that can be used to treat drug allergies, such as antihistamines (e.g., diphenhydramine) and corticosteroids, either individually or in combination.

[0206] anaphylaxis In some embodiments, T H The two-mediated condition includes anaphylaxis, and the additional therapeutic agent includes an agent that can be used to treat anaphylaxis, such as the same agent that can be used to treat allergies caused by food, insect venom, or drugs that can be used to treat anaphylaxis (e.g., epinephrine).

[0207] Eosinophilia In some embodiments, T H The 2-mediated condition includes eosinophilia (e.g., primary eosinophilia), and the additional therapeutic agent includes a drug that can be used to treat eosinophilia, such as a corticosteroid (e.g., prednisone).

[0208] These T H For each of the two-mediated conditions, in some embodiments, the pharmaceutical composition of the present disclosure may be administered in addition to one or more of the additional therapeutic agents provided, e.g., the pharmaceutical composition and the additional therapeutic agent may be co-administered.

[0209] T H Additional agents that may be useful in downregulating pathways involved in 2 cell activation include mepolizumab, lebrikizumab, tralokinumab, GSK3772847, RG6149 / AMG282, ANB020, OC000459, BI 671800, AZD1981, AS1517499, YM-341619, AS1810722, SB010, resiquimod, imiquimod, and CYT003.

[0210] Administration In certain aspects, provided herein are methods of delivering a pharmaceutical composition containing Prevotella bacteria described herein to a subject. In some embodiments of the methods provided herein, the composition is administered in conjunction with administration of an additional therapeutic agent (e.g., an anti-inflammatory agent). In some embodiments, the Prevotella bacteria are co-formulated with the additional therapeutic agent in a pharmaceutical composition. In some embodiments, the Prevotella bacteria (e.g., a pharmaceutical composition thereof) are co-administered with the additional therapeutic agent. In some embodiments, the additional therapeutic agent is administered to the subject prior to (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, or 55 minutes, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 hours, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days before) administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof). In some embodiments, the additional therapeutic agent is administered to the subject after administration of the Prevotella bacteria (e.g., a pharmaceutical composition thereof) (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, or 55 minutes, 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, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days). In some embodiments, the same delivery mode is used to deliver both the Prevotella bacteria (e.g., a pharmaceutical composition thereof) and the additional therapeutic agent. In some embodiments, different delivery modes are used to deliver the Prevotella bacteria (e.g., a pharmaceutical composition thereof) and the additional therapeutic agent. For example, in some embodiments, the Prevotella bacteria (e.g., a pharmaceutical composition thereof) is administered orally and the additional therapeutic agent is administered by injection (e.g., intravenous and / or intramuscular injection).

[0211] In certain embodiments, the pharmaceutical compositions and dosage forms described herein may be administered in conjunction with any other conventional treatments, which may be applied as needed and / or indicated, and which may occur before, simultaneously with, or after administration of the pharmaceutical compositions and dosage forms described herein.

[0212] The administration regimen can be any of a variety of methods and amounts and can be determined by those skilled in the art according to known clinical factors. As is known in the medical field, the dosage for any one patient can depend on many factors, such as the subject's species, size, body surface area, age, sex, immunocompetence, and overall health, the particular microorganism administered, the duration and route of administration, the type and stage of disease, and other compounds (e.g., co-administered drugs). In addition to the above factors, such levels can be affected by the infectivity and properties of the microorganism, as can be determined by those skilled in the art. The dosage of the pharmaceutical compositions described herein can be appropriately set or adjusted according to the dosage form, route of administration, the degree or stage of the condition, and the like. For example, a typical effective dose of a drug may range from 0.01 mg / kg body weight / day to 1000 mg / kg body weight / day, 0.1 mg / kg body weight / day to 1000 mg / kg body weight / day, 0.5 mg / kg body weight / day to 500 mg / kg body weight / day, 1 mg / kg body weight / day to 100 mg / kg body weight / day, or 5 mg / kg body weight / day to 50 mg / kg body weight / day, which may be, but is not limited to, 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.

[0213] In some embodiments, the dose administered to a subject is sufficient to prevent the condition, delay the onset of the condition, or slow or halt the progression of the condition, or prevent the recurrence of the condition. One of skill in the art will recognize that the dosage will depend on various factors (e.g., the potency of the particular compound used, and the age, species, condition, and weight of the subject). The size of the dose will also be determined by the route, timing, and frequency of administration, as well as the existence, nature, and extent of any adverse side effects and desired physiological effects that may accompany the administration of a particular compound.

[0214] Appropriate dosage and administration regimen can be determined by conventional range-finding techniques known to those skilled in the art.Generally, treatment is initiated with a lower dosage that is less than the appropriate dose of the compound.Then, this dosage is increased by small increments until the optimal effect is achieved under this situation.Effective dosage and treatment protocol can be determined by routine and conventional means, for example, by starting with a low dose in experimental animals, then increasing the dosage while monitoring the effect, and further systematically changing the dosage regimen.Generally, experimental animals are used to determine the maximum tolerated dose ("MTD") of bioactive agent per kilogram of body weight.Those skilled in the art regularly estimate dosage for efficacy while avoiding toxicity in other species, such as humans.

[0215] In accordance with the above, in therapeutic applications, dosages of active agents used in accordance with the present invention will 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 professional administering the treatment, among other factors that will affect the selected dosage. Generally, the dose should be sufficient to cause a delay in the progression of the condition, and preferably sufficient to cause regression.

[0216] Separate administrations can include any number of two or more administrations (doses), such as two, three, four, five, or six administrations. One of skill in the art can readily determine the number of administrations or the desirability of administering one or more additional administrations according to art-known methods for monitoring therapeutic methods and other monitoring methods provided herein. In some embodiments, the doses can be separated by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days, or 1, 2, 3, or 4 weeks. Thus, the methods provided herein include administering one or more administrations of bacteria to a subject, where the number of administrations can be determined by monitoring the subject and determining whether to administer one or more additional administrations based on the results of this monitoring. The decision to administer one or more additional doses may be based on various monitoring results (e.g., but not limited to, the subject's anti-bacterial antibody titer, the subject's overall health, and / or the subject's body weight).

[0217] The interval between doses can be any of a variety of time periods. This interval between doses can be a function of any of a variety of factors, including the number of doses, the time period for the subject to mount an immune response, and / or the time period for the subject to clear bacteria from normal tissues or the intestine, as described with respect to the monitoring step. In one example, this time period can be a function of the time period for the subject to mount an immune response, e.g., the time period can be longer than the time period for the subject to mount an immune response, e.g., greater than about 1 week, greater than about 10 days, greater than about 2 weeks, or greater than about 1 month. In another example, this time period can be shorter than the time period for the subject to mount an immune response, e.g., less than about 1 week, less than about 10 days, less than about 2 weeks, or less than about 1 month. In another example, this time period can be a function of the time period for the subject to clear bacteria from normal tissues or the intestine, e.g., the time period can be longer than the time period for the subject to clear bacteria from normal tissues or the intestine, e.g., greater than about 1 day, greater than about 2 days, greater than about 3 days, greater than about 5 days, or greater than about 1 week.

[0218] In some embodiments, delivery of an additional therapeutic agent in combination with the Prevotella bacteria described herein (e.g., pharmaceutical compositions thereof) reduces side effects and / or improves the efficacy of the additional therapeutic agent.

[0219] An effective dose of an additional therapeutic agent, as described herein, is an amount of the therapeutic agent effective to achieve the desired therapeutic response for a particular patient (e.g., subject), composition, and mode of administration, with minimal toxicity to the patient. Effective dosage levels can be determined using the methods described herein and will depend on various pharmacokinetic factors (e.g., the activity of the particular composition administered, the route of administration, the duration of administration, the rate of excretion of the particular compound used, the duration of treatment, other drugs, compounds, and / or substances used in combination with the particular composition used, the age, sex, weight, condition, overall health, and past medical history of the patient being treated, and similar factors known in the medical arts). Generally, an effective dose of an additional therapeutic agent will be the amount of the therapeutic agent that is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend on the factors described above.

[0220] Additional treatment toxicity refers to the level of side effects experienced by a subject during and after treatment. Adverse events associated with treatment toxicity include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, hair loss, anaphylaxis, anemia, anxiety, loss of appetite, joint pain, asthenia, ataxia, azotemia, lack of balance, bone pain, bleeding, blood clots, hypotension, hypertension, dyspnea, bronchitis, contusion, low white blood cell count, low red blood cell count, low platelet count, cardiac toxicity, cystitis, hemorrhagic cystitis, arrhythmia, valvular heart disease, cardiomyopathy, coronary artery disease, cataracts, central nervous system toxicity, and cognitive impairment. , confusion, conjunctivitis, constipation, cough, muscle cramps, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, indigestion, difficulty breathing, edema, electrolyte abnormalities, esophagitis, fatigue, lack of fertility, fever, flatulence, flushing, gastric reflux, gastroesophageal reflux disease, genital pain, granulocytopenia, gynecomastia, glaucoma, hair loss, hand-foot syndrome, headache, hearing loss, heart failure, heart palpitations, heartburn, hematoma, hemorrhagic cystitis, hepatotoxicity, hyperamylasemia, hypercalcemia, hyperchloremia, hyperglycemia, hyperkalemia Hyperlipemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hyperpigmentation, hypertriglyceridemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypochloremia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, erectile dysfunction, infection, injection site reaction, insomnia, iron deficiency, pruritus, arthralgia, renal failure, leukopenia, liver dysfunction, memory loss, menopause, sore mouth, mucositis, myalgia, bone marrow suppression, Myocarditis, neutropenic fever, nausea, nephrotoxicity, neutropenia, nosebleeds, numbness, ototoxicity, pain, palmar-plantar paresthesia, pancytopenia, pericarditis, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pneumonitis, interstitial pneumonitis, proteinuria, pulmonary embolism, pulmonary fibrosis, pulmonary toxicity, rash, rapid heartbeat, rectal bleeding, restlessness, rhinitis, seizures, shortness of breath, sinusitis, thrombocytopenia, tinnitus, urinary tract infection, vaginal bleeding, vaginal dryness, vertigo, water retention, weakness, weight loss, weight gain, and xerostomia. Generally, toxicity is acceptable if the benefit to the patient achieved through treatment outweighs the adverse events experienced by the patient due to treatment.

[0221] In some embodiments, the condition is treated by administration of Prevotella bacteria (eg, a pharmaceutical composition thereof).

[0222] As described herein, the condition to be treated is T H These may include 2-mediated conditions, such as atopic dermatitis and / or food allergies. [Example]

[0223] Example 1: Effect of Prevotella histicola in a contact hypersensitivity model using FITC Skin exposure to an antigen can over time trigger an allergic response to this antigen, for example, in the form of a skin allergy (e.g., dermatitis, or atopic dermatitis, or eczema) and / or in the form of a food allergy (see, e.g., Han et al. The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines. Immunol. Rev. 2017. July;278(1):116-130. Doi:10.1111 / imr.12546; Kawasaki et al. Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized mice. Allergy. 2018. June;73(6):1313-1321. Doi:10.1111 / all.13404; Martel et al. Translational animal models of atopic dermatitis for preclinical studies. Yale J. Biol. Med. 2017. Sept;90(3):389-402; Jin et al. Animal models of atopic dermatitis. J. Invest. Dermatol. 2009. Jan:129(1):31-40. Doi 10.1038 / jid.2008.106).

[0224] The effects of Prevotella histicola strain B 50329 have been studied in contact hypersensitivity models using fluorescein isothiocyanate (FITC) (e.g., Li et al. T-helper type-2 contact hypersensitivity of Balb / c mice aggravated by dibutyl phthalate via long-term dermal exposure. February 3, 2014. https: / / doi.org / 10.1371 / journal.pone.0087887; Imai et al. Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate. Clin. Exp. Allergy. 2006 Nov;36(11):1462-8; Dearman et al. Role of CD4+ T helper 2-type cells in cutaneous inflammatory responses induced by fluorescein isothiocynate. Immunology. 2000 Dec;101(4):442-451. Doi:10.1046 / j.1365-2567.2000.01126.x).

[0225] Prevotella histicola strain B 50329 was administered by oral gavage and the effect of Prevotella histicola on inflammation was analyzed using various readouts.

[0226] This study was carried out using microorganisms reconstituted from powder (e.g., lyophilized form of powder). Sucrose was used as the vehicle for reconstitution.

[0227] For each daily gavage, one vial of Prevotella histicola strain B 50329 and one vial of anaerobic sucrose were retrieved from the refrigerator. The appropriate bacterial solution was prepared in a sterile tube using the anaerobic sucrose. For example, 800 μl of sucrose was added to 80 mg of Prevotella histicola strain B 50329. To ensure proper resuspension, the vial of resuspended powder was vortexed to prevent the powder from adhering to the vial. Mice were gavaged with the resuspended powder at a volume of 100 μl per mouse immediately after vortexing (before the powder settled), and the remaining powder mixture was discarded (freshly prepared dilutions should be used each time). Negative control mice were gavaged with 100 μl of vehicle per day.

[0228] Hypersensitivity Study Protocol using FITC: Mice were purchased from Taconic and allowed to acclimate to the animal facility for at least one week before the start of the experiment. Mice were housed with five animals (or fewer) per cage, with each cage constituting a different treatment group.

[0229] On day 0, mice were anesthetized with isoflurane (one at a time) and the hair on their backs was shaved.

[0230] On day 1, a solution of 0.5% FITC (w / v) was dissolved in adjuvant (dibutyl phthalate (DBP)) and acetone (1:1). To prepare 0.5% FITC, 250 mg of FITC was dissolved in 25 ml of acetone. Once completely dissolved, 25 ml of DBP was added and mixed by vortexing.

[0231] On days 1 and 2, mice were sensitized by applying μl of 0.5% FITC solution to their backs with a pipette. Anaerobic sucrose served as a negative control. Dexamethasone served as a positive control (dexamethasone stock solution was prepared by resuspending 25 mg of dexamethasone (Sigma) in 1.6 ml of 96% ethanol).

[0232] On days 1–6, mice were gavaged with vehicle (negative control, group 1) or Prevotella histicola strain B 50329 (group 3), or injected intraperitoneally (i.p.) with dexamethasone (positive control, group 2), according to the study design described below.

[0233] [Table 22]

[0234] In addition to daily oral gavage (Groups 1 and 3) and IP injection (Group 2), mice were challenged on day 6 with FITC as follows: On day 6, each mouse was anesthetized with isoflurane, a baseline left ear measurement was obtained using a caliper, and then the left ear was painted with 20 μl of a 0.5% FITC solution (20 μl of 0.5% FITC (w / v) DBP:acetone (1.1)) ("ear challenge" or "FITC challenge").

[0235] On day 7, measurements were taken 8 hours after ear challenge using a caliper. Mice were euthanized and ears were harvested for downstream mRNA analysis using the TaqMan RNA-to-CT 1-Step Kit (Applied Biosystems, ThermoFisher Scientific catalog number 4392653) according to the manufacturer's instructions.

[0236] The results are shown in Figures 1A and 1B.

[0237] Oral administration of Prevotella histicola strain B 50329 (labeled "Prevotella histicola" in Figures 1A-1B) significantly reduced ear swelling 8 hours after FITC ear challenge (Figure 1A).

[0238] Compared to the vehicle group, Prevotella histicola strain B 50329 treatment reduced gene expression for IL-4, IL-5, IL-33, IL-17a, and TSLP in the ear (Figure 1B).

[0239] Example 2: Effect of Prevotella histicola in a contact hypersensitivity model using FITC The effect of Prevotella histicola strain B 50329 in a contact hypersensitivity model using FITC was tested against two other strains (strain 1 and strain 2), strain 1 being a strain of a Prevotella species other than histicola and strain 2 being a strain of a different genus than Prevotella.

[0240] On day 0, mice were anesthetized with isoflurane and their backs were shaved as described in Example 1. On days 1 and 2, mice were sensitized by applying 400 μl of 0.5% FITC solution to their backs with a pipette. On days 1 to 6, mice were gavaged with vehicle (sucrose) or the bacterial strains to be tested, or injected intraperitoneally (ip) with dexamethasone (positive control).

[0241] On day 6, each mouse was anesthetized with isoflurane and a baseline left ear measurement was obtained using a caliper as described in Example 1. The mice were then FITC challenged with 20 μl of a 0.5% FITC solution applied to the left ear.

[0242] On day 7, exactly 8 hours after challenge, mice were euthanized and post-challenge ear measurements were obtained using calipers.

[0243] The results are shown in Table 2. Oral administration of Prevotella histicola strain B 50329 (labeled "Prevotella histicola" in Figure 2) significantly reduced ear swelling 8 hours after FITC challenge, but two other bacterial strains (strains 1 and 2) did not (Figure 2). The difference in ear swelling between Prevotella histicola strain B 50329 and strain 1 (a strain from another species of Prevotella) was not statistically significant, but the difference in ear swelling between Prevotella histicola strain B 50329 and strain 2 (a strain from a different genus than Prevotella) was statistically significant.

[0244] Example 3: Effect of Prevotella histicola in the MC903 model of dermatitis-associated food allergy to the egg white protein ovalbumin (OVA) A mouse model of dermatitis-associated food allergy was used to evaluate the efficacy of the bacterial strains in modulating the allergic response.

[0245] The vitamin D3 analog MC903 induces inflammation and has been used in models of atopic dermatitis (e.g., Hussain et al. Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy. 2017. American Academy of Allergy, Asthma & Immunol. http: / / dx.doi.org / 10.1016 / j.jaci.2017.02.035; Moosbrugger-Martinz et al. A mouse model for atopic dermatitis using topical application of vitamin D3 or its analog MC903. Methods Mol. Biol. 2017;1559:91-106; Li et al. Topical vitamin D3 and low-calcium analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis). See dermatitis. PNAS. Aug. 1, 2006. Vol. 103(31):11736-11741).

[0246] Using MC903, mice can be epicutaneously sensitized to an antigen of interest, resulting in skin sensitization typified by the production of TCLP and IL-4 (see, e.g., Noti et al. Exposure to food allergens through inflamed skin promotes intestinal food allergy via the TSLP-basophil axis. J. Allergy Clin. Immunol. 2014 May;133(5):1390-1399.e6). The study design for the MC903 model of dermatitis-associated food allergy is shown in Figure 3A. The allergen to be tested (e.g., OVA) can be obtained from vendors such as Invivogen or Sigma.

[0247] Materials and Methods Female BALB / c mice (6-8 weeks old) were purchased from Taconic Farms. Animals were housed under specific pathogen-free conditions in the animal facility (five mice or fewer per cage), and all experiments were performed under protocols and guidelines approved by the Institutional Animal Care and Use Committee (IACUC). Mice were acclimated in the animal facility for one week prior to the start of the experiment. They were fed PicoLab Rodent Diet 20, provided autoclaved water ad libitum via sipper bottle, and checked daily.

[0248] To induce a mouse model mimicking egg food allergy, mice were exposed to MC903 (Tocris) and 100 μg of ovalbumin (OVA) daily for 14 consecutive days (days 1–14). 45 μM MC903 in 20 μL of 100% ethanol was applied to one ear with a pipette, and once the ear was dry, 100 μg of OVA in PBS was applied. 20 μL of ethanol was applied to the vehicle control ear.

[0249] For daily oral gavage treatments (days 1–17), negative control mice received vehicle (lyophilized sucrose) and positive control mice received tofacitinib (20 mg / kg (po) in 100 ul / mouse in 0.5% methylcellulose; Tocris). One group of mice received 10 mg of Prevotella histicola strain B 50329 daily (3.13E+09 TCC / dose), while the other group received 10 mg of either strain A (1.23E+10 TCC / dose) or strain B (7.83E+09 TCC / dose) (bacterial strains other than Prevotella histicola strain B 50329—strain A is a strain from a different genus than Prevotella, and strain B is a different strain of Prevotella histicola). On day 15, mice were challenged with 50 mg of OVA by oral gavage (po, also called intragastric (ig)).

[0250] On day 17.5, mice received a second oral challenge with 50 mg of OVA, after which ear inflammation was measured using a caliper.

[0251] Ear inflammation on day 18 (12 hours after the second OVA challenge) is shown in Figure 3B. Treatment with Prevotella histicola strain B 50329 (labeled "P. histicola" in Figures 3B-3D) significantly reduced ear inflammation compared to the negative control group.

[0252] On day 18, 12 hours after the second OVA challenge, mice were euthanized. Blood (for serum) and tissues (e.g., spleen, draining cervical lymph nodes, mesenteric lymph nodes, and ears) were collected and processed ex vivo.

[0253] Sera were analyzed by ELISA for anti-OVA IgG1 and anti-OVA IgE using Chondrex, Inc. Mouse Anti-OVA IgG1 Antibody Assay Kit (Cat. No. 3013) and Mouse Anti-OVA IgE Antibody Assay Kit (Cat. No. 3010). The results are shown in Figure 3C.

[0254] Ears were homogenized for cytokine detection. Spleens, mesenteric lymph nodes (mLN), and cervical lymph nodes (cLN) were analyzed for cytokine expression after in vitro PMA stimulation and supernatant collection. Single-cell suspensions of tissues were prepared, counted, plated at 200,000 cells / well, and restimulated with PMA / ionomycin (eBiosciences Cell Stimulation Cocktail, Catalog No. 00-4975) for 48 hours according to the manufacturer's instructions. Supernatants were collected for downstream multiplex ELISA to determine cytokine levels using the Meso Scale Discovery (MSD) kit (Cat. No. K15068L-2). Similarly, ears were dissociated in 250 μl of T-PER buffer (Thermo Scientific Catalog No. 78510) containing Halt Protease (Thermo Scientific Catalog No. 78444), and protein concentration was quantified using a BCA kit (Thermo Scientific Catalog No. 23227). Cytokine levels were quantified using an MSD kit (Cat. No. K15068L-2) using 100 μg of protein. Results are shown in Figure 3D.

[0255] Example 4: Effect of Prevotella histicola in the MC903 model of type 2 (Th2) immune response in food allergy to OVA and complete peanut protein (CPE) To induce mouse models mimicking egg and peanut food allergy, mice were sensitized to food allergens as described in Example 3 and depicted in Figure 4A.

[0256] MC903 was prepared in EtOH and applied daily as indicated (days 1–14).

[0257] Some mice were challenged daily for 14 consecutive days with MC903 and 100 μg of OVA in PBS. Other mice were challenged daily for 14 consecutive days with MC903 and 100 μg of complete peanut protein (CPE). In addition to application of antigen (e.g., OVA or CPE), mice were gavaged with sucrose vehicle (negative control), tofacitinib (positive control), bacterial strain A (10 mg / dose), or Prevotella histicola strain B 50329 (10 mg / dose). Strain A is a strain from a different genus than Prevotella.

[0258] On day 15, mice were challenged by oral gavage with either 50 mg OVA or 50 mg peanut powder.

[0259] On day 17.5, mice were challenged a second time by oral gavage with either 50 mg OVA or 50 mg whole peanut flour (CPE).

[0260] On day 18, 12 hours after the final antigen challenge, ear thickness was measured. Mice were euthanized and serum and tissues were collected as described in Example 3.

[0261] As shown in Figure 4B, Prevotella histicola strain B 50329 (labeled "P. histicola" in Figures 4B-4D) significantly reduced ear inflammation in both the OVA and peanut allergy (CPE) groups compared with the vehicle control group. Antibody analysis (anti-OVA IgG1 and anti-OVA IgE) was performed as described in Example 3, and the results are shown in Figure 4C. Cytokine analysis was performed as described in Example 3, and the results are shown in Figure 4D. Ear RNA was measured as described in Example 1, and the results are shown in Figure 4E.

[0262] Example 5: Atopic Dermatitis and Anaphylaxis with MC903 To induce mouse models mimicking egg food allergy, peanut allergy, and / or other allergens of interest, mice were sensitized to food allergens as described in Example 3 and depicted in FIG. 5.

[0263] MC903 was prepared in EtOH and applied daily as indicated (days 1–14).

[0264] Some mice were exposed to MC903 and 100 μg of CPE in PBS daily for up to 30 consecutive days. In addition to application of the model antigen (e.g., CPE), mice were gavaged with sucrose vehicle (negative control), tofacitinib (positive control; 100 μl orally daily), bacterial strain A (10 mg / dose), Prevotella histicola strain B 50329 (10 mg / dose), or 200 μg / mouse of anti-IL-4 (ip on days 3, 6, 9, and 12; BioXcell) (on days 1–17 or 1–30).

[0265] On day 30, mice were challenged with 500ug CPE ip and observed for anaphylaxis. Body temperature was measured using a rectal thermometer 30 minutes after CPE challenge.

[0266] On day 31, mice were sacrificed and ear inflammation was measured. Cytokines in the spleen, ear, and lymphoid tissue were analyzed using the methods described in Examples 1 and 3.

[0267] Example 6: Tape-stripping peanut allergy model As discussed above, various animal models exist for studying food allergy. Some of these models induce allergen (e.g., antigen) sensitization through a skin barrier defect (see, e.g., Ohsaki et al. Maternal IgG immune complexes induce food allergen-specific tolerance in offspring. J Exp Med. 2018. 215:91-113; Kanagaratham et al. Experimental models for studying food allergy. Cell Mol Gastroenterol Hepatol. 2018. 6(3):356-369. e1. Doi:10.1016 / j.jcmgh.2018.05.010). In some models, a skin barrier defect is induced by repeatedly shaving the fur and then tape-stripping the skin, and the allergen is then applied to the resulting damaged skin. This "cutaneous sensitization" to the allergen is followed at some point by an intragastric challenge with the allergen. For example, as shown in Figure 6A, mice can be sensitized on the ear or back using tape stripping and exposure to peanut antigen on either days 1, 2, and 3 (ear sensitization) or days 0, 3, and 6 (back sensitization). For the ear sensitization group, mice are tape stripped on day 0 only, while for the back sensitization group, tape stripping is performed on days 0, 3, and 6. Mice can be challenged on day 21 and immediately thereafter observed and / or sacrificed for various readouts (e.g., but not limited to, measurement of serum peanut-specific IgE, IgG1, and IgA, as well as total IgE, IgG1, and IgA, body temperature, anaphylaxis scoring, diarrhea scoring, and / or ex vivo restimulation of mesenteric lymph node (MLN) cells) to assess various cytokines (e.g., IL-4, IL-5, and TSLP). Alternatively, serum can be collected on day 35 (see Figure 6B), and in other cases, studies can be conducted over 65 days (see Figure 6C). Mice can be scored for anaphylaxis and diarrhea as shown in Tables 3 and 4, respectively.

[0268] [Table 23]

[0269] [Table 24]

[0270] Female BLAB / c mice were purchased from Taconic Farms, and all experiments were performed under protocols and guidelines approved by the Institutional Animal Care and Use Committee (IACUC).

[0271] Mice were acclimated in the animal facility for one week prior to the start of the experiment. All mice were housed in individually ventilated cages with standard bedding and enrichment, with no more than five mice per cage. They were fed PicoLab Rodent Diet 20 and provided autoclaved water via sipper bottle ad libitum and checked daily.

[0272] Experimental design Animal groups were divided as follows (5 mice / group): 1) Naive mice (no sensitization, no peanut challenge); 2) naive mice (no sensitization, peanut challenge on day 21); 3) ear sensitization (sensitized on days 1, 2, and 3) (no challenge); 4) ear sensitization (sensitization on days 1, 2, and 3) (peanut challenge on day 21); 5) ear sensitization (sensitization on days 1, 2, and 3) (tofacitinib 20 mg / kg) (peanut challenge on day 21); 6) ear sensitization (sensitization on days 1, 2, and 3) (10 mg of P. histicola) (peanut challenge on day 21); 7) back sensitization (sensitized on days 0, 3, and 6) (no challenge); 8) back sensitization (sensitization on days 0, 3, and 6) (peanut challenge on day 21); 9) Back sensitization (sensitization on days 0, 3, and 6) (tofacitinib 20 mg / kg) (peanut challenge on day 21); and 10) Back sensitization (sensitization on days 0, 3, and 6) (Prevotella histicola strain B 50329 10 mg) (peanut challenge on day 21).

[0273] On day 0, mice were individually anesthetized with isoflurane. For the ear-sensitized group, the ears of each mouse were repeatedly stripped with cellophane tape (approximately 7-8 times). For the back-sensitized group, the hair on the back was shaved and stripped with cellophane tape (approximately 7-8 times).

[0274] For the ear sensitization group, mice were tape stripped on day 0. On days 1, 2, and 3, 25 μl of peanut protein solution (4 mg / ml peanut protein in PBS) was applied to both ears with a cotton swab.

[0275] For the back sensitization group, the mice were tape stripped and 100 μg of peanut protein was applied on days 0, 3, and 6. The sensitized area was covered with a new waterproof bandage each time.

[0276] For the Prevotella histicola strain B 50329 group, mice were gavaged with 10 mg of bacteria on days 1–21.

[0277] On day 21, mice from groups 2, 4, 5, 6, 8, and 9 were challenged by oral gavage with 100 mg of peanut protein. Mice from all groups were cheek bled 1 hour after peanut protein challenge and blood was collected for total IgE, peanut-specific IgE, total IgG1, peanut-specific IgG1, total IgA, and peanut-specific IgA ELISA (Chondrex, according to the manufacturer's instructions).

[0278] Inflammation results are shown in Figure 6D. For both the ear and back groups, Prevotella histicola strain B 50329 (labeled "P. histicola" in Figures 6D-6I) reduced inflammation.

[0279] Total and peanut-specific serum IgE and IgG1 levels from the day of challenge are shown in Figures 6E and 6F, respectively.

[0280] Total and peanut-specific serum IgE, IgG1, and IgA levels from 2 weeks post-challenge are shown in Figures 6G, 6H, and 6I, respectively.

[0281] Example 7: FITC-CHS model Prevotella histicola strain B 50329 was tested in the FITC-CHS model, as shown in Figure 7A. The dose tested was 4.69E+09 TCC.

[0282] On day 7, the effect of Prevotella histicola strain B50329 on TH2 cytokines (IL-13, IL-4, IL-5, IL-31, and IL-33) was examined. As shown in Figure 7B, Prevotella histicola strain B50329 (labeled "Prevotella histicola" in Figures 7B-7C) significantly reduced the levels of IL-13, IL-5, and IL-31 in the gut-draining mesenteric lymph nodes. Cytokine levels were determined by MSD, and the experiment was performed as described in Example 3. As shown in Figure 7C, Prevotella histicola strain B50329 treatment significantly reduced the levels of IL-13 in the ear-draining cervical lymph nodes. The experiment was carried out as described in Example 3.

[0283] This example demonstrates that treatment with Prevotella histicola strain B 50329 increases T cell proliferation in PMA / ionomycin ex vivo restimulated cells from gut-draining mesenteric lymph nodes and ear-draining cervical lymph nodes. H 2 cytokine secretion was demonstrated to be significantly reduced.

[0284] Example 8: Atopic Dermatitis with MC903 Prevotella histicola strain B 50329 was tested in an atopic dermatitis model using MC903, as shown in Figure 8A.

[0285] For this experiment, mice were purchased from Taconic Labs and acclimated to the animal facility for one week prior to the start of the experiment. Mice were housed in individually ventilated cages with standard bedding and enrichment, with five animals per cage. Standard Purina rodent diet (5001) and autoclaved water were provided ad libitum and checked daily.

[0286] On day 1, mice were anesthetized and baseline ear measurements were obtained. Then, while anesthetized, ears were sensitized with 45 nM calcipitriol (MC903) by pipetting a total of 20 μL of solution onto both the dorsal and anterior ears. Ears were sensitized daily for 14 days.

[0287] On days 1–14, mice were administered Prevotella histicola strain B 50329 at a dose of 4.69E+09 TCC or a positive control (tofacitinib) QD by oral gavage daily.

[0288] Ear measurements were taken throughout the study to track changes in thickness over time, and on day 14, the change in ear thickness from baseline was determined.

[0289] On day 17, ex vivo experiments were performed.

[0290] MC903 Preparation Protocol: 10 mg of calcipitriol powder was dissolved in 10 mL of 99% ethanol to make a 1 mg / mL stock. The stock was diluted to 0.01856 mg / mL with 99% ethanol. This diluted solution was aliquoted into light-proof tubes for routine use at -20°C.

[0291] Preparation of positive control - tofacitinib: Tofacitinib was prepared in 0.5% (w / v) methylcellulose. Purified water was brought to a boil on a stirring / heating plate. The appropriate amount of powdered methylcellulose was weighed out. The boiling water was stirred and the powdered methylcellulose was added. Stirring continued until the powder was incorporated into the water. The mixture was cooled overnight at 4°C while stirring on a stirring plate. A 50 mg stock of tofacitinib was resuspended in 0.5% MC (the mixture formed a suspension). Tofacitinib was administered po at 100uL per mouse.

[0292] result: As shown in Figure 8B, Prevotella histicola strain B 50329 (labeled "Prevotella histicola" in Figures 8B-8E) treatment reduced ear inflammation in MC903 atopic dermatitis, as determined by ear measurements over time (left panel) and ear inflammation at day 14 (right panel).

[0293] The effect of Prevotella histicola strain B 50329 on TH2 cytokine transcript levels (Tslp, Il5, Il31, Il4, Ccl19, and Ccr4) in ear tissue was examined on day 17. As shown in Figure 8C, Prevotella histicola strain B 50329 treatment readily reduced the levels of Il5, Il31, and Ccr4 transcripts in ear tissue, as determined by qPCR.

[0294] The effect of Prevotella histicola strain B 50329 on mast cell-related gene transcript levels (Mcpt1) in the jejunum was examined on day 17. The results in Figure 8D demonstrate that Prevotella histicola strain B 50329 significantly reduced Mcpt1 transcript levels in the jejunum of mice in the MC903 atopic dermatitis model, as determined by qPCR.

[0295] On day 17, the effect of Prevotella histicola strain B 50329 on IL-10 levels in the mesenteric lymph nodes and spleen was examined. As shown in Figure 8E, treatment with Prevotella histicola strain B 50329 significantly increased IL-10 levels in the mesenteric lymph nodes and spleen of mice upon ex vivo restimulation with PMA / ionomycin in tissues isolated from atopic dermatitis using MC903, as determined by MSD. This experiment was performed as described in Example 3.

[0296] The results of this example demonstrate that ear inflammation in atopic dermatitis using MC903 was significantly reduced by treatment with Prevotella histicola strain B 50329 compared to vehicle-treated mice.

[0297] Prevotella histicola strain B 50329 treatment showed a decrease in TH2 cytokine transcripts in ear tissue and a mast cell-associated transcript (Mcpt1) in the jejunum.

[0298] Prevotella histicola strain B 50329 treatment resulted in elevated levels of IL-10 in gut-draining mesenteric lymph nodes and spleen cells upon ex vivo restimulation with PMA / ionomycin.

[0299] Incorporation by Reference All publications and patent applications mentioned herein are incorporated by reference in their entirety as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including all definitions herein, will control.

[0300] equivalent Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein which equivalents are intended to be encompassed by the claims appended hereto. The present invention encompasses, for example, the following embodiments: [Embodiment 1] T in a subject H 2. A method for treating or preventing a Prevotella-mediated condition, comprising administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria. [Embodiment 2] The method of embodiment 1, wherein the subject is a human subject. [Embodiment 3] The method of embodiment 1 or 2, wherein at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial content of the pharmaceutical composition is derived from Prevotella bacteria. [Embodiment 4] The method comprises: H 4. The method of any one of embodiments 1-3, wherein a 2-mediated condition is treated. [Embodiment 5] The T H 5. The method of any one of embodiments 1-4, wherein the 2-mediated condition is asthma, atopic dermatitis, eosinophilic disease, and / or allergy. [Embodiment 6] T H 6. The method of embodiment 5, wherein the two-mediated condition is an allergy, and the allergy is a food allergy, seasonal allergic rhinitis, and / or a pet allergy. [Embodiment 7] The T H 6. The method of embodiment 5, wherein the 2-mediated condition is atopic dermatitis. [Embodiment 8] The T H 6. The method of embodiment 5, wherein the 2-mediated condition is a food allergy. [Embodiment 9] The method of embodiment 8, wherein the food allergy is a peanut allergy, a milk allergy, an egg allergy, a fish allergy, a shellfish allergy, a tree nut allergy, a wheat allergy, or a soy allergy. [Embodiment 10] The method of embodiment 8, wherein the food allergy is a peanut allergy. [Embodiment 11] The method of embodiment 8, wherein the food allergy is an allergy to a food antigen. [Embodiment 12] The method described in embodiment 11, wherein the food antigen is a peanut antigen, a milk antigen, a chicken egg antigen, a fish antigen, a crustacean antigen, a nut antigen, a wheat antigen, or a soybean antigen. [Embodiment 13] The method described in embodiment 11, wherein the food antigen is a peanut antigen. [Embodiment 14] The method of any one of embodiments 1 to 13, wherein the method reduces interleukin (IL)-4 levels in the subject. [Embodiment 15] The method described in embodiment 14, wherein the IL-4 level is an IL-4 protein level or an IL-4 mRNA level. [Embodiment 16] The method of any one of embodiments 1 to 15, wherein the method reduces interleukin (IL)-5 levels in the subject. [Embodiment 17] The method described in embodiment 16, wherein the IL-5 level is an IL-5 protein level or an IL-5 mRNA level. [Embodiment 18] The method of any one of embodiments 1 to 17, wherein the method reduces interleukin (IL)-13 levels in the subject. [Embodiment 19] The method described in embodiment 18, wherein the IL-13 level is an IL-13 protein level or an IL-13 mRNA level. [Embodiment 20] The method of any one of embodiments 1 to 19, wherein the method reduces interleukin (IL)-19 levels in the subject. [Embodiment 21] The method described in embodiment 20, wherein the IL-19 level is an IL-19 protein level or an IL-19 mRNA level. [Embodiment 22] The method of any one of embodiments 1 to 21, wherein the method reduces interleukin (IL)-21 levels in the subject. [Embodiment 23] The method described in embodiment 22, wherein the IL-21 level is an IL-21 protein level or an IL-21 mRNA level. [Embodiment 24] The method of any one of embodiments 1 to 23, wherein the method reduces interleukin (IL)-31 levels in the subject. [Embodiment 25] The method described in embodiment 24, wherein the IL-31 level is an IL-31 protein level or an IL-31 mRNA level. [Embodiment 26] The method of any one of embodiments 1 to 25, wherein the method reduces interleukin (IL)-33 levels in the subject. [Embodiment 27] The method described in embodiment 26, wherein the IL-33 level is an IL-33 protein level or an IL-33 mRNA level. [Embodiment 28] The method of any one of embodiments 1 to 27, wherein the method reduces thymic stromal lymphopoietin (TSLP) levels in the subject. [Embodiment 29] The method described in embodiment 28, wherein the TSLP level is a TSLP protein level or a TSLP mRNA level. [Embodiment 30] The method described in any one of embodiments 1 to 29, wherein the method reduces IgG1 levels in the subject. [Embodiment 31] The method described in embodiment 30, wherein the IgG1 level is an IgG1 protein level or an IgG1 mRNA level. [Embodiment 32] The method described in any one of embodiments 1 to 31, wherein the method reduces IgE levels in the subject. [Embodiment 33] The method described in embodiment 32, wherein the IgE level is an IgE protein level or an IgE mRNA level. [Embodiment 34] The method described in any one of embodiments 1 to 33, wherein the method reduces IgA levels in the subject. [Embodiment 35] The method described in embodiment 34, wherein the IgA level is an IgA protein level or an IgA mRNA level. [Embodiment 36] The Prevotella bacterium is selected from the group consisting of Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, and Prevotella histicola. histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea stercorea), Prevotella tannerae, Prevotella timonensis, Prevotella jejunijejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanseiensis 36. The method of any of embodiments 1-35, wherein the bacterium is selected from the group consisting of Prevotella nanceiensis, Prevotella oryzae, Prevotella paludiviens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, and / or Prevotella veroralis. [Embodiment 37] The method of embodiment 36, wherein the Prevotella bacterium is Prevotella histicola. [Embodiment 38] The method of any one of embodiments 1 to 37, wherein the Prevotella bacterium is a strain that contains at least 95% genomic sequence identity, 16S sequence identity, and / or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). [Embodiment 39] The method of embodiment 38, wherein the Prevotella bacterium is a strain that contains at least 99% genomic sequence identity, 16S sequence identity, and / or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 40] The method of embodiment 39, wherein the Prevotella bacterium is Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 41] The method described in any one of embodiments 1 to 40, wherein the Prevotella bacterium is a strain of Prevotella bacterium that includes one or more proteins listed in Table 1. [Embodiment 42] The method of any one of embodiments 1 to 41, wherein the Prevotella bacterium is a strain of Prevotella that is substantially free of the proteins listed in Table 2. [Embodiment 43] The method of any one of embodiments 1 to 42, wherein the pharmaceutical composition comprises live bacteria, killed bacteria, or attenuated bacteria. [Embodiment 44] The method of any one of embodiments 1 to 42, wherein the Prevotella bacteria are gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated, and / or oxygen-sparged. [Embodiment 45] The method of embodiment 44, wherein the Prevotella bacteria have been heat-inactivated at 50°C for 2 hours or at 90°C for 2 hours. [Embodiment 46] The method of embodiment 44, wherein the Prevotella bacteria have been oxygen sparged at 0.1 vvm for 2 hours. [Embodiment 47] The method described in any one of embodiments 1 to 46, wherein the Prevotella bacteria are freeze-dried Prevotella bacteria. [Embodiment 48] The method of embodiment 47, wherein the composition further comprises a pharmaceutically acceptable excipient. [Embodiment 49] The method described in any one of embodiments 1 to 48, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species. [Embodiment 50] The method described in any one of embodiments 1 to 48, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. [Embodiment 51] The method of any one of embodiments 1 to 48, wherein the Prevotella bacteria in the pharmaceutical composition are derived from various species. [Embodiment 52] The method described in any one of embodiments 1 to 49, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. [Embodiment 53] The method of any one of embodiments 1 to 52, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent. [Embodiment 54] The method of embodiment 53, wherein the additional therapeutic agent is an anti-inflammatory agent. [Embodiment 55] The method of any one of embodiments 1 to 54, wherein the pharmaceutical composition is formulated as a solid dosage form. [Embodiment 56] The method of embodiment 55, wherein the solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof. [Embodiment 57] The method of embodiment 55 or 56, wherein the solid dosage form further comprises a pharmaceutically acceptable excipient. [Embodiment 58] The method of any one of embodiments 55 to 57, wherein the solid dosage form comprises an enteric coating. [Embodiment 59] The method of any one of embodiments 55 to 58, wherein the solid dosage form is formulated for oral administration. [Embodiment 60] The method of any one of embodiments 1 to 54, wherein the pharmaceutical composition is formulated as a suspension. [Embodiment 61] The method of embodiment 60, wherein the suspension is formulated for oral administration. [Embodiment 62] The method described in embodiment 60 or 61, wherein the suspension comprises PBS, optionally containing sucrose or glucose. [Embodiment 63] The method of embodiment 60, wherein the suspension is formulated for intravenous administration. [Embodiment 64] The method of embodiment 60, wherein the suspension is formulated for intraperitoneal administration. [Embodiment 65] The method described in embodiment 63 or 64, wherein the suspension comprises PBS. [Embodiment 66] The method of embodiment 60, wherein the pharmaceutical composition is administered intravenously. [Embodiment 67] The method of embodiment 60, wherein the pharmaceutical composition is administered by injection, for example, by subcutaneous injection, intradermal injection, or intraperitoneal injection. [Embodiment 68] The method described in any one of embodiments 60 to 67, wherein the suspension further contains a pharmaceutically acceptable additive. [Embodiment 69] The method described in any one of embodiments 60 to 68, wherein the suspension further contains a buffer. [Embodiment 70] The method described in embodiment 69, wherein the buffer solution is PBS. [Embodiment 71] The method described in any one of embodiments 1 to 70, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents. [Embodiment 72] The method of embodiment 71, wherein the one or more additional therapeutic agents are one or more anti-inflammatory agents. [Embodiment 73] The method of any one of embodiments 1 to 62 or 68 to 72, wherein the pharmaceutical composition is administered orally. [Embodiment 74] The method described in any one of embodiments 1 to 73, wherein the pharmaceutical composition contains about 5 mg to about 900 mg of total protein as determined by Bradford assay or BCA assay. [Embodiment 75] The method of any one of embodiments 1 to 74, wherein the pharmaceutical composition comprises about 10 mg of Prevotella bacteria as determined by Bradford assay or BCA assay. [Embodiment 76] The method of any one of embodiments 1 to 75, further comprising administering an additional therapeutic agent to the subject. [Embodiment 77] The method of embodiment 76, wherein the additional therapeutic agent is an anti-inflammatory agent. [Embodiment 78] The method of embodiment 76, wherein the additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukotriene receptor antagonist, an antibody, or a combination thereof. [Embodiment 79] The method of embodiment 76 or 77, wherein the pharmaceutical composition comprises the additional therapeutic agent. [Embodiment 80] The method of embodiment 76, wherein the additional therapeutic agent is an antibiotic agent. [Embodiment 81] T in a subject H 2. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria for use in the treatment or prevention of a HIV-2 mediated condition. [Embodiment 82] The pharmaceutical composition described in embodiment 81, wherein the subject is a human subject. [Embodiment 83] A pharmaceutical composition described in embodiment 81 or 82, wherein at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial content of the pharmaceutical composition is derived from Prevotella bacteria. [Embodiment 84] The pharmaceutical composition comprises the T H 84. The pharmaceutical composition of any of embodiments 81-83, for treating a 2-mediated condition. [Embodiment 85] The T H 85. The pharmaceutical composition of any of embodiments 81-84, wherein the 2-mediated condition is asthma, atopic dermatitis, eosinophilic disease, and / or allergy. [Embodiment 86] T H The pharmaceutical composition of embodiment 85, wherein the two-mediated condition is an allergy, and said allergy is a food allergy, seasonal allergic rhinitis, and / or a pet allergy. [Embodiment 87] The T H The pharmaceutical composition of embodiment 85, wherein the 2-mediated condition is atopic dermatitis. [Embodiment 88] The T H The pharmaceutical composition of embodiment 85, wherein the 2-mediated condition is a food allergy. [Embodiment 89] The pharmaceutical composition of embodiment 88, wherein the food allergy is peanut allergy, milk allergy, chicken egg allergy, fish allergy, shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. [Embodiment 90] The pharmaceutical composition described in embodiment 88, wherein the food allergy is peanut allergy. [Embodiment 91] The pharmaceutical composition described in embodiment 88, wherein the food allergy is an allergy to a food antigen. [Embodiment 92] The pharmaceutical composition of embodiment 91, wherein the food antigen is a peanut antigen, a milk antigen, a chicken egg antigen, a fish antigen, a crustacean antigen, a nut antigen, a wheat antigen, or a soybean antigen. [Embodiment 93] The pharmaceutical composition of embodiment 91, wherein the food antigen is a peanut antigen. [Embodiment 94] The pharmaceutical composition of any one of embodiments 81 to 93, wherein administration of the pharmaceutical composition reduces interleukin (IL)-4 levels in the subject. [Embodiment 95] The pharmaceutical composition described in embodiment 94, wherein the IL-4 level is an IL-4 protein level or an IL-4 mRNA level. [Embodiment 96] The pharmaceutical composition of any one of embodiments 81 to 95, wherein administration of the pharmaceutical composition reduces interleukin (IL)-5 levels in the subject. [Embodiment 97] The pharmaceutical composition described in embodiment 96, wherein the IL-5 level is an IL-5 protein level or an IL-5 mRNA level. [Embodiment 98] The pharmaceutical composition of any one of embodiments 81 to 97, wherein administration of the pharmaceutical composition reduces interleukin (IL)-13 levels in the subject. [Embodiment 99] The pharmaceutical composition described in embodiment 98, wherein the IL-13 level is an IL-13 protein level or an IL-13 mRNA level. [Embodiment 100] A pharmaceutical composition described in any one of embodiments 81 to 99, wherein administration of the pharmaceutical composition reduces interleukin (IL)-19 levels in the subject. [Embodiment 101] The pharmaceutical composition of embodiment 100, wherein the IL-19 level is an IL-19 protein level or an IL-19 mRNA level. [Embodiment 102] The pharmaceutical composition of any one of embodiments 81 to 101, wherein administration of the pharmaceutical composition reduces interleukin (IL)-21 levels in the subject. [Embodiment 103] The pharmaceutical composition of embodiment 102, wherein the IL-21 level is the IL-21 protein level or the IL-21 mRNA level. [Embodiment 104] The pharmaceutical composition of any one of embodiments 81 to 103, wherein administration of the pharmaceutical composition reduces interleukin (IL)-31 levels in the subject. [Embodiment 105] The pharmaceutical composition described in embodiment 104, wherein the IL-31 level is the IL-31 protein level or the IL-31 mRNA level. [Embodiment 106] The pharmaceutical composition of any one of embodiments 81 to 105, wherein administration of the pharmaceutical composition reduces interleukin (IL)-33 levels in the subject. [Embodiment 107] The pharmaceutical composition described in embodiment 106, wherein the IL-33 level is an IL-33 protein level or an IL-4 mRNA level. [Embodiment 108] A pharmaceutical composition described in any of embodiments 81 to 107, wherein administration of the pharmaceutical composition reduces thymic stromal lymphopoietin (TSLP) levels in the subject. [Embodiment 109] The pharmaceutical composition of embodiment 108, wherein the TSLP level is a TSLP protein level or a TSLP mRNA level. [Embodiment 110] The pharmaceutical composition of any one of embodiments 81 to 109, wherein administration of the pharmaceutical composition reduces IgG1 levels in the subject. [Embodiment 111] The pharmaceutical composition described in embodiment 110, wherein the IgG1 level is an IgG1 protein level or an IgG1 mRNA level. [Embodiment 112] The pharmaceutical composition of any one of embodiments 81 to 111, wherein administration of the pharmaceutical composition reduces IgE levels in the subject. [Embodiment 113] The pharmaceutical composition described in embodiment 112, wherein the IgE level is an IgE protein level or an IgE mRNA level. [Embodiment 114] A pharmaceutical composition described in any one of embodiments 81 to 113, wherein administration of the pharmaceutical composition reduces IgA levels in the subject. [Embodiment 115] The pharmaceutical composition described in embodiment 114, wherein the IgA level is an IgA protein level or an IgA mRNA level. [Embodiment 116] The Prevotella bacterium is selected from the group consisting of Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, and Prevotella histicola. histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea stercorea), Prevotella tannerae, Prevotella timonensis, Prevotella jejunijejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanseiensis 116. The pharmaceutical composition according to any of embodiments 81 to 115, wherein the bacterium selected from the group consisting of Prevotella nanceiensis, Prevotella oryzae, Prevotella paludiviens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, and / or Prevotella veroralis. [Embodiment 117] The pharmaceutical composition of embodiment 116, wherein the Prevotella bacterium is Prevotella histicola. [Embodiment 118] The pharmaceutical composition of any one of embodiments 81 to 117, wherein the Prevotella bacterium is a strain that contains at least 95% genomic sequence identity, 16S sequence identity, and / or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL Accession No. B 50329). [Embodiment 119] The pharmaceutical composition of embodiment 118, wherein the Prevotella bacterium is a strain that contains at least 99% genomic sequence identity, 16S sequence identity, and / or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 120] The pharmaceutical composition of embodiment 119, wherein the Prevotella bacterium is Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 121] A pharmaceutical composition described in any one of embodiments 81 to 120, wherein the Prevotella bacterium is a strain of Prevotella bacterium that contains one or more proteins listed in Table 1. [Embodiment 122] The pharmaceutical composition of any one of embodiments 81 to 121, wherein the Prevotella bacterium is a strain of Prevotella that is substantially free of the proteins listed in Table 2. [Embodiment 123] The pharmaceutical composition of any one of embodiments 81 to 122, wherein the pharmaceutical composition comprises live bacteria, killed bacteria, or attenuated bacteria. [Embodiment 124] The pharmaceutical composition of any one of embodiments 81 to 122, wherein the Prevotella bacteria are gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated, and / or oxygen-sparged. [Embodiment 125] The pharmaceutical composition of embodiment 124, wherein the Prevotella bacteria are heat-inactivated at 50°C for 2 hours or at 90°C for 2 hours. [Embodiment 126] The pharmaceutical composition of embodiment 124, wherein the Prevotella bacteria have been oxygen sparged at 0.1 vvm for 2 hours. [Embodiment 127] The pharmaceutical composition of any one of embodiments 81 to 126, wherein the Prevotella bacteria are freeze-dried Prevotella bacteria. [Embodiment 128] The pharmaceutical composition described in embodiment 127, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient. [Embodiment 129] A pharmaceutical composition described in any one of embodiments 81 to 128, wherein the Prevotella bacteria in the pharmaceutical composition are derived from the same species. [Embodiment 130] The pharmaceutical composition of any one of embodiments 81 to 128, wherein the Prevotella bacteria in the pharmaceutical composition are derived from the same strain. [Embodiment 131] A pharmaceutical composition described in any one of embodiments 81 to 128, wherein the Prevotella bacteria in the pharmaceutical composition are derived from various species. [Embodiment 132] The pharmaceutical composition of any one of embodiments 81 to 129, wherein the Prevotella bacteria in the pharmaceutical composition are derived from the same strain. [Embodiment 133] The pharmaceutical composition described in any one of embodiments 81 to 132, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent. [Embodiment 134] The pharmaceutical composition of embodiment 133, wherein the additional therapeutic agent is an anti-inflammatory agent. [Embodiment 135] The pharmaceutical composition described in any one of embodiments 81 to 134, wherein the pharmaceutical composition is formulated as a solid dosage form. [Embodiment 136] The pharmaceutical composition of embodiment 135, wherein the solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof. [Embodiment 137] The pharmaceutical composition of embodiment 135 or 136, wherein the solid dosage form further comprises a pharmaceutically acceptable excipient. [Embodiment 138] A pharmaceutical composition described in any one of embodiments 135 to 137, wherein the solid dosage form comprises an enteric coating. [Embodiment 139] A pharmaceutical composition described in any one of embodiments 135 to 138, wherein the solid dosage form is formulated for oral administration. [Embodiment 140] The pharmaceutical composition described in any one of embodiments 81 to 134, wherein the pharmaceutical composition is formulated as a suspension. [Embodiment 141] The pharmaceutical composition described in embodiment 140, wherein the suspension is formulated for oral administration. [Embodiment 142] The pharmaceutical composition of embodiment 140 or 141, wherein the suspension comprises PBS, optionally containing sucrose or glucose. [Embodiment 143] The pharmaceutical composition described in embodiment 140, wherein the suspension is formulated for intravenous administration. [Embodiment 144] The pharmaceutical composition of embodiment 140, wherein the suspension is formulated for intraperitoneal administration. [Embodiment 145] The pharmaceutical composition of embodiment 143 or 144, wherein the suspending agent comprises PBS. [Embodiment 146] The pharmaceutical composition described in embodiment 140, wherein the pharmaceutical composition is administered intravenously. [Embodiment 147] The pharmaceutical composition of embodiment 140, wherein the pharmaceutical composition is administered by injection, for example, by subcutaneous injection, intradermal injection, or intraperitoneal injection. [Embodiment 148] A pharmaceutical composition described in any one of embodiments 140 to 147, wherein the suspension further contains a pharmaceutically acceptable additive. [Embodiment 149] The pharmaceutical composition described in any one of embodiments 140 to 148, wherein the suspension further contains a buffer solution. [Embodiment 150] The pharmaceutical composition of embodiment 149, wherein the buffer solution is PBS. [Embodiment 151] The pharmaceutical composition described in any one of embodiments 81 to 150, further comprising one or more additional therapeutic agents. [Embodiment 152] The pharmaceutical composition of embodiment 151, wherein the one or more additional therapeutic agents are one or more anti-inflammatory agents. [Embodiment 153] The pharmaceutical composition described in any one of embodiments 81 to 142 or 148 to 152, wherein the pharmaceutical composition is administered orally. [Embodiment 154] The pharmaceutical composition of any of embodiments 81 to 153, wherein the pharmaceutical composition contains from about 5 mg to about 900 mg of total protein as determined by Bradford assay or BCA assay. [Embodiment 155] The pharmaceutical composition of any one of embodiments 81 to 154, wherein the pharmaceutical composition contains approximately 10 mg of Prevotella bacteria as determined by Bradford assay or BCA assay. [Embodiment 156] The pharmaceutical composition described in any one of embodiments 81 to 155, wherein the pharmaceutical composition is administered to the subject together with an additional therapeutic agent. [Embodiment 157] The pharmaceutical composition of embodiment 156, wherein the additional therapeutic agent is an anti-inflammatory agent. [Embodiment 158] The pharmaceutical composition of embodiment 156, wherein the additional therapeutic agent is a corticosteroid, an antihistamine, a mast cell stabilizer, a decongestant, a leukotriene receptor antagonist, an antibody, or a combination thereof. [Embodiment 159] The pharmaceutical composition described in embodiment 156 or 157, wherein the pharmaceutical composition comprises the additional therapeutic agent. [Embodiment 160] The pharmaceutical composition described in embodiment 156, wherein the additional therapeutic agent is an antibiotic agent. [Embodiment 161] T in the subject H 2. Use of a pharmaceutical composition comprising a therapeutically effective amount of Prevotella bacteria for the manufacture of a medicament for the treatment or prevention of a mediated condition. [Embodiment 162] The use described in embodiment 161, wherein the subject is a human subject. [Embodiment 163] The use described in embodiment 161 or 162, wherein at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial content of the pharmaceutical composition is derived from Prevotella bacteria. [Embodiment 164] The use H The use according to any of embodiments 161 to 163, wherein a 2-mediated condition is treated. [Embodiment 165] The TH The use according to any of embodiments 161 to 164, wherein the 2-mediated condition is asthma, atopic dermatitis, eosinophilic disease, and / or allergy. [Embodiment 166] T H The use according to embodiment 165, wherein the two-mediated condition is an allergy, and said allergy is a food allergy, seasonal allergic rhinitis, and / or a pet allergy. [Embodiment 167] The T H The use according to embodiment 165, wherein the 2-mediated condition is atopic dermatitis. [Embodiment 168] The T H The use according to embodiment 165, wherein the 2-mediated condition is a food allergy. [Embodiment 169] The use described in embodiment 168, wherein the food allergy is peanut allergy, milk allergy, chicken egg allergy, fish allergy, shellfish allergy, tree nut allergy, wheat allergy, or soy allergy. [Embodiment 170] The use described in embodiment 168, wherein the food allergy is peanut allergy. [Embodiment 171] The use described in embodiment 168, wherein the food allergy is an allergy to a food antigen. [Embodiment 172] The use of embodiment 171, wherein the food antigen is a peanut antigen, a milk antigen, a chicken egg antigen, a fish antigen, a crustacean antigen, a nut antigen, a wheat antigen, or a soybean antigen. [Embodiment 173] The use described in embodiment 171, wherein the food antigen is a peanut antigen. [Embodiment 174] The use described in any of embodiments 161 to 173, wherein administration of the pharmaceutical composition reduces interleukin (IL)-4 levels in the subject. [Embodiment 175] The use described in embodiment 174, wherein the IL-4 level is an IL-4 protein level or an IL-4 mRNA level. [Embodiment 176] The use described in any of embodiments 161 to 175, wherein administration of the pharmaceutical composition reduces interleukin (IL)-5 levels in the subject. [Embodiment 177] The use described in embodiment 176, wherein the IL-5 level is an IL-5 protein level or an IL-5 mRNA level. [Embodiment 178] The use described in any of embodiments 161 to 177, wherein administration of the pharmaceutical composition reduces interleukin (IL)-13 levels in the subject. [Embodiment 179] The use described in embodiment 178, wherein the IL-13 level is an IL-13 protein level or an IL-13 mRNA level. [Embodiment 180] The use described in any of embodiments 161 to 179, wherein administration of the pharmaceutical composition reduces interleukin (IL)-19 levels in the subject. [Embodiment 181] The use described in embodiment 180, wherein the IL-19 level is an IL-19 protein level or an IL-19 mRNA level. [Embodiment 182] The use described in any of embodiments 161 to 181, wherein administration of the pharmaceutical composition reduces interleukin (IL)-21 levels in the subject. [Embodiment 183] The use described in embodiment 182, wherein the IL-21 level is the IL-21 protein level or the IL-21 mRNA level. [Embodiment 184] The use described in any of embodiments 161 to 183, wherein administration of the pharmaceutical composition reduces interleukin (IL)-31 levels in the subject. [Embodiment 185] The use described in embodiment 184, wherein the IL-31 level is the IL-31 protein level or the IL-31 mRNA level. [Embodiment 186] The use described in any of embodiments 161 to 185, wherein administration of the pharmaceutical composition reduces interleukin (IL)-33 levels in the subject. [Embodiment 187] The use described in embodiment 186, wherein the IL-33 level is an IL-33 protein level or an IL-4 mRNA level. [Embodiment 188] The use described in any of embodiments 161 to 187, wherein administration of the pharmaceutical composition reduces thymic stromal lymphopoietin (TSLP) levels in the subject. [Embodiment 189] The use described in embodiment 188, wherein the TSLP level is a TSLP protein level or a TSLP mRNA level. [Embodiment 190] The use described in any of embodiments 161 to 189, wherein administration of the pharmaceutical composition reduces IgG1 levels in the subject. [Embodiment 191] The use described in embodiment 190, wherein the IgG1 level is an IgG1 protein level or an IgG1 mRNA level. [Embodiment 192] The use described in any of embodiments 161 to 191, wherein administration of the pharmaceutical composition reduces IgE levels in the subject. [Embodiment 193] The use described in embodiment 192, wherein the IgE level is an IgE protein level or an IgE mRNA level. [Embodiment 194] The use described in any of embodiments 161 to 193, wherein administration of the pharmaceutical composition reduces IgA levels in the subject. [Embodiment 195] The use described in embodiment 194, wherein the IgA level is an IgA protein level or an IgA mRNA level. [Embodiment 196] The Prevotella bacterium is selected from the group consisting of Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, and Prevotella histicola. histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea stercorea), Prevotella tannerae, Prevotella timonensis, Prevotella jejunijejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanseiensis Use according to any of embodiments 161 to 195, wherein the bacterium selected from the group consisting of Prevotella nanceiensis, Prevotella oryzae, Prevotella paludiviens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, and / or Prevotella veroralis. [Embodiment 197] The use of embodiment 196, wherein the Prevotella bacterium is Prevotella histicola. [Embodiment 198] The use of any one of embodiments 161 to 197, wherein the Prevotella bacterium is a strain that contains at least 95% genomic sequence identity, 16S sequence identity, and / or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 199] The use of embodiment 198, wherein the Prevotella bacterium is a strain that contains at least 99% genomic sequence identity, 16S sequence identity, and / or CRISPR sequence identity to the nucleotide sequence of Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 200] The use of embodiment 199, wherein the Prevotella bacterium is Prevotella strain B 50329 (NRRL accession number B 50329). [Embodiment 201] The use described in any of embodiments 161 to 200, wherein the Prevotella bacterium is a strain of Prevotella bacterium that contains one or more proteins listed in Table 1. [Embodiment 202] The use of any of embodiments 161 to 201, wherein the Prevotella bacterium is a strain of Prevotella that is substantially free of the proteins listed in Table 2. [Embodiment 203] The use of any of embodiments 161 to 202, wherein the pharmaceutical composition comprises live bacteria, killed bacteria, or attenuated bacteria. [Embodiment 204] The use of any one of embodiments 161 to 202, wherein the Prevotella bacteria are gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated, and / or oxygen-sparged. [Embodiment 205] The use of embodiment 204, wherein the Prevotella bacteria have been heat-inactivated at 50°C for 2 hours or at 90°C for 2 hours. [Embodiment 206] The use of embodiment 204, wherein the Prevotella bacteria have been oxygen sparged at 0.1 vvm for 2 hours. [Embodiment 207] The use described in any one of embodiments 161 to 206, wherein the Prevotella bacteria are freeze-dried Prevotella bacteria. [Embodiment 208] The use described in embodiment 207, wherein the composition further comprises a pharmaceutically acceptable additive. [Embodiment 209] The use described in any one of embodiments 161 to 208, wherein the Prevotella bacteria in the pharmaceutical composition are from the same species. [Embodiment 210] The use described in any one of embodiments 161 to 208, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. [Embodiment 211] The use described in any of embodiments 161 to 208, wherein the Prevotella bacteria in the pharmaceutical composition are derived from various species. [Embodiment 212] The use described in any one of embodiments 161 to 209, wherein the Prevotella bacteria in the pharmaceutical composition are from the same strain. [Embodiment 213] The use described in any one of embodiments 161 to 212, wherein the pharmaceutical composition is administered in combination with an additional therapeutic agent. [Embodiment 214] The use described in embodiment 213, wherein the additional therapeutic agent is an anti-inflammatory agent. [Embodiment 215] The use described in any one of embodiments 161 to 214, wherein the pharmaceutical composition is formulated as a solid dosage form. [Embodiment 216] The use described in embodiment 215, wherein the solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof. [Embodiment 217] The use described in embodiment 215 or 216, wherein the solid dosage form further comprises a pharmaceutically acceptable excipient. [Embodiment 218] The use described in any one of embodiments 215 to 217, wherein the solid dosage form comprises an enteric coating. [Embodiment 219] The use described in any of embodiments 215 to 218, wherein the solid dosage form is formulated for oral administration. [Embodiment 220] The use described in any one of embodiments 161 to 214, wherein the pharmaceutical composition is formulated as a suspension. [Embodiment 221] The use described in embodiment 220, wherein the suspension is formulated for oral administration. [Embodiment 222] The use described in embodiment 220 or 221, wherein the suspension comprises PBS, optionally containing sucrose or glucose. [Embodiment 223] The use described in embodiment 220, wherein the suspension is formulated for intravenous administration. [Embodiment 224] The use described in embodiment 220, wherein the suspension is formulated for intraperitoneal administration. [Embodiment 225] The use described in embodiment 223 or 224, wherein the suspension comprises PBS. [Embodiment 226] The use described in embodiment 220, wherein the pharmaceutical composition is administered intravenously. [Embodiment 227] The use described in embodiment 220, wherein the pharmaceutical composition is administered by injection, for example, by subcutaneous injection, intradermal injection, or intraperitoneal injection. [Embodiment 228] The use described in any of embodiments 220 to 227, wherein the suspension further contains a pharmaceutically acceptable additive. [Embodiment 229] The use described in any of embodiments 220 to 228, wherein the suspension further contains a buffer solution. [Embodiment 230] The use described in embodiment 229, wherein the buffer solution is PBS. [Embodiment 231] The use described in any of embodiments 161 to 230, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents. [Embodiment 232] The use described in embodiment 231, wherein the one or more additional therapeutic agents are one or more anti-inflammatory agents. [Embodiment 233] The use described in any one of embodiments 161 to 222 or 228 to 232, wherein the pharmaceutical composition is administered orally. [Embodiment 234] The use described in any of embodiments 161 to 233, wherein the pharmaceutical composition contains about 5 mg to about 900 mg of total protein as determined by Bradford assay or BCA assay. [Embodiment 235] The use described in any of embodiments 161 to 234, wherein the pharmaceutical composition contains approximately 10 mg of Prevotella bacteria as determined by Bradford assay or BCA assay.

Claims

1. T in the subject H 1. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella histicola bacteria for use in the treatment or prevention of a T H 2-mediated condition, wherein the Prevotella histicola bacteria is Prevotella strain B 50329 (NRRL Accession No. B 50329) bacteria, and the T H 2-mediated condition is selected from asthma, atopic dermatitis, eosinophilic disease, and / or allergy.

2. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella histicola bacteria for use in treating or preventing a T H 2-mediated condition in a subject, wherein the Prevotella histicola bacteria is Prevotella strain B 50329 (NRRL Accession No. B 50329) bacteria, and the T H 2-mediated condition is atopic dermatitis or a food allergy.

3. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella histicola bacteria for use in treating or preventing a T H 2 mediated condition in a subject, wherein the Prevotella histicola bacteria is Prevotella strain B 50329 (NRRL Accession No. B 50329) bacteria, the T H 2 mediated condition is selected from asthma, atopic dermatitis, eosinophilic disease, and / or allergy, and the Prevotella histicola bacteria is the only active ingredient present in the pharmaceutical composition.

4. A pharmaceutical composition comprising a therapeutically effective amount of Prevotella histicola bacteria for use in treating or preventing a T H 2 mediated condition in a subject, wherein the Prevotella histicola bacteria is Prevotella strain B 50329 (NRRL Accession No. B 50329) bacteria, the T H 2 mediated condition is atopic dermatitis or a food allergy, and the Prevotella histicola bacteria is the only active ingredient present in the pharmaceutical composition.

5. 10. The pharmaceutical composition of claim 1, wherein at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the microbial content of the pharmaceutical composition is derived from Prevotella histicola bacteria.

6. Said T H 6. The pharmaceutical composition of any one of claims 1, 3 and 5, wherein the 2-mediated condition is atopic dermatitis and / or allergy.

7. Said T H 7. The pharmaceutical composition of claim 6, wherein the two-mediated condition is an allergy, optionally wherein the allergy is a food allergy, seasonal allergic rhinitis, and / or a pet allergy.

8. Said T H 8. The pharmaceutical composition of claim 7, wherein the two-mediated condition is a food allergy, optionally wherein the food allergy is a peanut allergy, a milk allergy, a chicken egg allergy, a fish allergy, a shellfish allergy, a tree nut allergy, a wheat allergy, or a soy allergy.

9. Administering the pharmaceutical composition to the subject (a) the level of interleukin (IL)-4 in the subject is reduced; (b) the level of IL-5 in the subject is reduced. (c) reducing the level of IL-13 in the subject; (d) the level of IL-19 in the subject is reduced. (e) the level of IL-21 in the subject is reduced. (f) the level of IL-31 in the subject is reduced. (g) reducing the level of IL-33 in the subject. (h) reducing thymic stromal lymphopoietin (TSLP) levels in the subject; (i) the level of IgG1 in the subject is reduced; (j) reducing IgE levels in the subject; and / or (k) reducing IgA levels in the subject; The pharmaceutical composition according to any one of claims 1 to 8.

10. 10. The pharmaceutical composition of any one of claims 1 to 9, wherein the Prevotella histicola bacteria are live, killed, or attenuated, and optionally the Prevotella histicola bacteria are gamma-irradiated, UV-irradiated, heat-inactivated, acid-treated, and / or oxygen-sparged.

11. 11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the Prevotella histicola bacteria are freeze-dried Prevotella histicola bacteria.

12. The pharmaceutical composition of claim 11, further comprising a pharmaceutically acceptable excipient.

13. 13. The pharmaceutical composition of any one of claims 1 to 12, wherein the pharmaceutical composition is formulated for oral administration as a solid dosage form, optionally wherein the solid dosage form is a tablet, mini-tablet, capsule, pill, or powder, or a combination thereof.

14. 14. The pharmaceutical composition of claim 13, wherein the solid dosage form further comprises a pharmaceutically acceptable excipient.

15. 15. The pharmaceutical composition of claim 13 or 14, wherein the solid dosage form comprises an enteric coating.

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