Probiotic and prebiotic compositions, and methods of use thereof for treatment and prevention of graft verses host disease

Abstract

Probiotic compositions containing non-pathogenic microbial entities, e.g., bacterial or fungal entities, are described herein. The probiotic compositions may optionally contain or be used in conjunction with one or more prebiotics. Uses of the probiotic compositions to treat or prevent transplant disorders, e.g., graft-versus-host disease (GVHD), in a subject are also provided.

1 - 123 . (canceled) 
     
     
         124 . A method of decreasing a Th-1-related pro-inflammatory cytokine response in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutical composition, wherein the pharmaceutical composition comprises a population of bacteria of a species selected from the group consisting of  Ruminococcus gnavus, Eubacterium rectale, Blautia luti, Blautia wexlerae , and combinations thereof, and a pharmaceutical excipient, such that the Th-1 related pro-inflammatory cytokine response in the human subject is decreased. 
     
     
         125 . The method of  claim 124 , wherein the population of bacteria is of the species  Ruminococcus gnavus.    
     
     
         126 . The method of  claim 124 , wherein the population of bacteria is of the species  Eubacterium rectale.    
     
     
         127 . The method of  claim 124 , wherein the population of bacteria is of the species  Blautia luti.    
     
     
         128 . The method of  claim 124 , wherein the population of bacteria is of the species  Blautia wexlerae.    
     
     
         129 . The method of  claim 124 , wherein the proportion of Th-1 cells in the human subject is decreased. 
     
     
         130 . The method of  claim 129 , wherein the Th-1 cells are CXCR3+CCR6 −  T cells. 
     
     
         131 . The method of  claim 129 , wherein the proportion of Th-1 cells is decreased systemically. 
     
     
         132 . The method of  claim 129 , wherein the proportion of Th-1 cells is decreased in the gastrointestinal tract of the human subject. 
     
     
         133 . The method of  claim 129 , wherein the human subject has an autoimmune or an inflammatory disorder. 
     
     
         134 . The method of  claim 133 , wherein the autoimmune or inflammatory disorder is selected from the group consisting of acute disseminated encephalomyelitis, acute necrotizing hemorrhagic leukoencephalitis, Addison's disease, adhesive capsulitis, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM nephritis, anti-TBM nephritis, antiphospholipid syndrome, arthofibrosis, atrial fibrosis, autoimmune angioedema, autoimmune aplastic anemia, autoimmune dusautonomia, autoimmune hepatitis, autoimmune hyperlipidemia, autoimmune immunodeficiency, autoimmune inner ear disease, autoimmune myocarditis, autoimmune oophoritis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune thrombocytopenic purpura, autoimmune thyroid disease, autoimmune urticaria, axonal and neuronal neuropathies, balo disease, Behcet's disease, benign mucosal pemphigoid, Bullous pemphigoid, cardiomyopathy, castleman disease, celiac disease, chagas disease, chronic fatigue syndrome, chronic inflammatory demyelinating polyneuropathy, chronic Lyme disease, chronic recurrent multifocal osteomyelitis, Churg-Strauss syndrome, cicatricial pemphigoid, cirrhosis, cogans syndrome, cold agglutinin disease, congenital heart block, coxsackle myocarditis, CREST disease, Crohn's disease, cystic fibrosis, essential mixed cryoglobulinemia, deficiency of the interleukin-1 receptor antagonist, demyelinating neuropathies, dermatitis herpetiformis, dermatomyosis, Devic's disease, discoid lupus, Dressier's syndrome, Dupuytren's contracture, endometriosis, endomyocardial fibrosis, eosinophilic esophagitis, eosinophilic facsciitis, erythema nodosum, experimental allergic encephalomyelitis, Evans syndrome, familial mediterranean fever, fibromyalgia, fibrosing alveolitis, giant cell arteritis, giant cell myocarditis, glomerulonephritis, Goodpasture's syndrome, graft-versus-host disease (GVHD), granulomatosus with polyanglitis, Graves' disease, Guillain-Bare syndrome, Hashimoto's encephalitis, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schonlein purpura, hepatitis, herpes gestationis, hypogammaglobulinemia, idiopathic thrombocytopenic purpura, IgA nephropathy, IgG4-related sclerosing disease, immunoregulatory lipoproteins, inclusion body myositis, inflammatory bowel disorders, interstitial cystitis, juvenile arthritis, juvenile myositis, Kawasaki syndrome, keloid, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA disease, mediastinal fibrosis, Meniere's disease, microscopic polyanglitis, mixed connective tissue disease, Mooren's ulcer, Mucha-Hamermann disease, multiple sclerosis (MS), myasthenia gravis, myelofibrosis, myositis, narcolepsy, neonatal onset multisystem inflammatory disease, nephrogenic systemic fibrosis, neutropenia, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), ocular-cicatricial pemphigoid, optic neuritis, palindromic rheumatism, pediatric autoimmune neuropsychiatric disorders associated with  streptococcus  (PANDAS), paraneoplastic cerebellar degeneration, paroxysmal nocturnal nemoglobinuria, Parry Romberg syndrome, Parsonnage-Turner syndrome, pars planitis, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia, Peyronie's disease, POEMS syndrome, polyarteritis nodosa, progressive massive fibrosis, tumor necrosis factor receptor-associated periodic syndrome, type I autoimmune polyglandular syndrome, type II autoimmune polyglandular syndrome, type III autoimmune polyglandular syndrome, polymyalgia rhematica, polymyositis, postmyocardial infarction syndrome, postpericardiotomy syndrome, progesterone dermatitis, primary biliary cirrhosis, primary sclerosing cholangitis, psoriasis, psoriatic arthritis, idiopathic pulmonary fibrosis, pyoderma gangrenosum, pure red cell aplasia, Raynauds phenomenon, reactic arthritis, reflex sympathetic dystrophy, Reiter's syndrome, relapsing polychondritis, restless legs syndrome, retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjogren's syndrome, sperm and testicular autoimmunity, stiff person syndrome, subacute bacterial endocarditis, Susac's syndrome, sympathetic ophthalmia, systemic lupus erythematosus (SLE), Takayasu's arthritis, temporal arteritis, thrombocytopenic purpura, Tolosa-Hunt syndrome, transverse myelitis, type 1 diabetes, ulcerative colitis, undifferentiated connective tissue disease, uveitis, vasculitis, vesiculobullous dermatosis, and vitiligo. 
     
     
         135 . The method of  claim 124 , wherein the cytokine response comprises release of a pro-inflammatory cytokine selected from the group consisting of interferon gamma (IFN-γ), interleukin-12 p70 (IL-12p70), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α) by an immune cell of the human subject. 
     
     
         136 . A method of increasing the proportion of Th-2 cells in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutical composition, wherein the pharmaceutical composition comprises a population of bacteria of a species selected from the group consisting of  Ruminococcus gnavus, Eubacterium  rectale,  Blautia wexlerae, Ruminococcus obeum, Blautia producta, Blautia hansenii , and combinations thereof, and a pharmaceutical excipient, such that the proportion of Th-2 cells in the human subject is increased. 
     
     
         137 . The method of  claim 136 , wherein the population of bacteria is of the species  Ruminococcus gnavus.    
     
     
         138 . The method of  claim 136 , wherein the population of bacteria is of the species  Eubacterium rectale.    
     
     
         139 . The method of  claim 136 , wherein the population of bacteria is of the species  Blautia wexlerae.    
     
     
         140 . The method of  claim 136 , wherein the population of bacteria is of the species  Ruminococcus obeum.    
     
     
         141 . The method of  claim 136 , wherein the population of bacteria is of the species  Blautia producta.    
     
     
         142 . The method of  claim 136 , wherein the population of bacteria is of the species  Blautia hansenii.    
     
     
         143 . The method of  claim 136 , wherein the Th-2 cells are CXCR3-CCR6-T cells. 
     
     
         144 . The method of  claim 136 , wherein the proportion of Th-2 cells is increased systemically. 
     
     
         145 . The method of  claim 136 , wherein the proportion of Th-2 cells is increased in the gastrointestinal tract of the human subject. 
     
     
         146 . The method of  claim 136 , wherein the human subject has an autoimmune or an inflammatory disorder. 
     
     
         147 . The method of  claim 146 , wherein the autoimmune or inflammatory disorder is selected from the group consisting of acute disseminated encephalomyelitis, acute necrotizing hemorrhagic leukoencephalitis, Addison's disease, adhesive capsulitis, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM nephritis, anti-TBM nephritis, antiphospholipid syndrome, arthofibrosis, atrial fibrosis, autoimmune angioedema, autoimmune aplastic anemia, autoimmune dusautonomia, autoimmune hepatitis, autoimmune hyperlipidemia, autoimmune immunodeficiency, autoimmune inner ear disease, autoimmune myocarditis, autoimmune oophoritis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune thrombocytopenic purpura, autoimmune thyroid disease, autoimmune urticaria, axonal and neuronal neuropathies, balo disease, Behcet's disease, benign mucosal pemphigoid, Bullous pemphigoid, cardiomyopathy, castleman disease, celiac disease, chagas disease, chronic fatigue syndrome, chronic inflammatory demyelinating polyneuropathy, chronic Lyme disease, chronic recurrent multifocal osteomyelitis, Churg-Strauss syndrome, cicatricial pemphigoid, cirrhosis, cogans syndrome, cold agglutinin disease, congenital heart block, coxsackle myocarditis, CREST disease, Crohn's disease, cystic fibrosis, essential mixed cryoglobulinemia, deficiency of the interleukin-1 receptor antagonist, demyelinating neuropathies, dermatitis herpetiformis, dermatomyosis, Devic's disease, discoid lupus, Dressier's syndrome, Dupuytren's contracture, endometriosis, endomyocardial fibrosis, eosinophilic esophagitis, eosinophilic facsciitis, erythema nodosum, experimental allergic encephalomyelitis, Evans syndrome, familial mediterranean fever, fibromyalgia, fibrosing alveolitis, giant cell arteritis, giant cell myocarditis, glomerulonephritis, Goodpasture's syndrome, graft-versus-host disease (GVHD), granulomatosus with polyanglitis, Graves' disease, Guillain-Bare syndrome, Hashimoto's encephalitis, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schonlein purpura, hepatitis, herpes gestationis, hypogammaglobulinemia, idiopathic thrombocytopenic purpura, IgA nephropathy, IgG4-related sclerosing disease, immunoregulatory lipoproteins, inclusion body myositis, inflammatory bowel disorders, interstitial cystitis, juvenile arthritis, juvenile myositis, Kawasaki syndrome, keloid, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA disease, mediastinal fibrosis, Meniere's disease, microscopic polyanglitis, mixed connective tissue disease, Mooren's ulcer, Mucha-Hamermann disease, multiple sclerosis (MS), myasthenia gravis, myelofibrosis, myositis, narcolepsy, neonatal onset multisystem inflammatory disease, nephrogenic systemic fibrosis, neutropenia, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), ocular-cicatricial pemphigoid, optic neuritis, palindromic rheumatism, pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS), paraneoplastic cerebellar degeneration, paroxysmal nocturnal nemoglobinuria, Parry Romberg syndrome, Parsonnage-Turner syndrome, pars planitis, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia, Peyronie's disease, POEMS syndrome, polyarteritis nodosa, progressive massive fibrosis, tumor necrosis factor receptor-associated periodic syndrome, type I autoimmune polyglandular syndrome, type II autoimmune polyglandular syndrome, type III autoimmune polyglandular syndrome, polymyalgia rhematica, polymyositis, postmyocardial infarction syndrome, postpericardiotomy syndrome, progesterone dermatitis, primary biliary cirrhosis, primary sclerosing cholangitis, psoriasis, psoriatic arthritis, idiopathic pulmonary fibrosis, pyoderma gangrenosum, pure red cell aplasia, Raynauds phenomenon, reactic arthritis, reflex sympathetic dystrophy, Reiter's syndrome, relapsing polychondritis, restless legs syndrome, retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjogren's syndrome, sperm and testicular autoimmunity, stiff person syndrome, subacute bacterial endocarditis, Susac's syndrome, sympathetic ophthalmia, systemic lupus erythematosus (SLE), Takayasu's arthritis, temporal arteritis, thrombocytopenic purpura, Tolosa-Hunt syndrome, transverse myelitis, type 1 diabetes, ulcerative colitis, undifferentiated connective tissue disease, uveitis, vasculitis, vesiculobullous dermatosis, and vitiligo.