THERAPEUTIC MICROBIOTA FOR THE TREATMENT AND/OR PREVENTION OF FOOD ALLERGY
Disclosed are methods and compositions for the prevention and treatment of food allergy. In particular, described herein are microbial consortia, including minimal microbial consortia, that can prevent and/or cure food allergy. In certain embodiments, the consortia comprise certain members of the taxa Clostridiales and/or Bacteroidetes.
1 . A pharmaceutical composition comprising:
(i) a preparation comprising a minimal microbial consortium consisting essentially of four to eleven strains of viable gut bacteria, in an amount sufficient to increase immune system tolerance when administered to an individual in need thereof, and
(ii) a pharmaceutically acceptable carrier.
2 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral delivery.
3 . The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition is in the oral dosage form of a capsule, a reconstituted lyophilisate, a food item, or is formulated as a liquid, gel, or fluid-gel.
4 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria consisting essentially of strains of Clostridium or Bacteroides.
5 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria consisting essentially of strains of Clostridium.
6 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria consisting essentially of strains of Bacteroides.
7 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria comprise Clostridium ramosum, Clostridium scindens, Clostridium hiranonsis, Clostridium bifermentans, Clostridium leptum, Clostridium sardiniensis, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides ovatus, Parabacteroides goldsteinii , or Prevotella tannerae.
8 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria comprise Clostridium ramosum, Clostridium scindens, Clostridium hiranonsis, Clostridium bifermentans, Clostridium leptum , or Clostridium sardiniensis.
9 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria comprise Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides ovatus, Parabacteroides goldsteinii , or Prevotella tannerae.
10 . The pharmaceutical composition of claim 1 , wherein the four to eleven strains of viable gut bacteria are in an amount are sufficient to treat or prevent a food allergy.
11 . The pharmaceutical composition of claim 1 , wherein four to eleven strains of viable gut bacteria are present in substantially equal biomass.
12 . The pharmaceutical composition of claim 1 , wherein four to eleven strains of viable gut bacteria are each present in an amount of at least about 1×108 CFUs/ml.
13 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition does not comprise any of the Species Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Bilophila wadsworthia, Alistipes onderdonkii, Desulfovibrio species, Lactobacillus johnsonii , or Parasutterella excrementihominis.
14 . The pharmaceutical composition of claim 1 , wherein minimal microbial consortium consisting essentially of four to eleven strains of viable gut bacteria is present in an amount sufficient to increase the proportion of T regulatory cells in a subject.
15 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that expresses exopolysaccharide, lipoteichoic acid (LTA), lipopolysaccharide (LPS) or other microbial adjuvant molecules that promote the development of regulatory T cells (Treg).
16 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that produces butyrate and/or propionate fermentation products via fermentation of carbohydrates and other carbon sources in the gut lumen.
17 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium performs the full complement of bile acid transformations.
18 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that produces compounds capable of stimulating the aryl hydrocarbon receptor (AhR) receptor pathway in gut epithelial cells, antigen presenting cells and/or T cells to stimulate development of regulatory T cell responses.
19 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that produces compounds capable of stimulating the pregnane X receptor with beneficial effects upon gut barrier function and/or development of regulatory T cell responses.
20 . The pharmaceutical composition of claim 19 , wherein the viable, culturable, anaerobic gut bacterial strain expresses desmolase or hydroxysteroid dehydrogenase.
21 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that produces compounds capable of stimulating the RORgamma (RAR-related orphan receptor gamma) pathways to stimulate development of regulatory T cell responses via direct stimulation or RORgamma-activated pathways in gut antigen presenting cells and/or epithelial cells that then stimulate regulatory T cell responses.
22 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that stimulates host production of mucins and complex glycoconjugates that improve gut barrier function and colonization by protective commensal species.
23 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that alters the gut luminal environment to reduce the deleterious activities of dysbiotic species promoting development of unhealthy allergic T cell responses to food antigens
24 . The pharmaceutical composition of claim 1 , wherein the minimal microbial consortium comprises a viable, culturable, anaerobic gut bacterial strain that alters the gut luminal environment to promote improved colonization by other members of the administered consortium for any of the above stated effects, and/or colonization by existing beneficial species in the patients underlying microbiota.
25 . A method for increasing immune system tolerance, comprising administering the pharmaceutical composition of claim 1 to a subject in need thereof.
26 . The method of claim 25 , wherein the pharmaceutical composition is formulated for oral delivery.
27 . The method of claim 25 , administration of the pharmaceutical composition is in an amount sufficient to treat or prevent a food allergy.