Bifidobacterium in the treatment of inflammatory disease

Abstract

A strain of Bifidobacterium isolated from resected and washed human gastrointestinal tract is significantly immunomodulatory following oral consumption in humans. The strain is useful in the prophylaxis and/or treatment of undesirable inflammatroy activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer.

1 . A strain of Bifidobacterium isolated from resected and washed human gastrointestinal tract which is significantly immunomodulatory following oral consumption in humans.  
     
     
         2 . A strain of Bifidobacterium as claimed in  claim 1  which effects changes in an immunological marker when introduced into a system comprising cells which interact with the immune system and cells of the immune system.  
     
     
         3 . A strain of Bifidobacterium as claimed in  claim 2  wherein the cells which interact with the immune system are epithelial cells.  
     
     
         4 . A strain of Bifidobacterium as claimed in  claim 2  or  3  wherein the immunological marker is a cytokine.  
     
     
         5 . A strain of Bifidobacterium as claimed in  claim 4  wherein the cytokine is TNFα.  
     
     
         6 . A strain of Bifidobacterium as claimed in any of  claims 2  to  5  wherein the cells which interact with the immune system and the immune system cells are of matched origin.  
     
     
         7 . A strain of Bifidobacterium as claimed in any of  claims 2  to  6  wherein the cells which interact with the immune system are of gastrointestinal, respiratory or genitourinary origin.  
     
     
         8 . A strain of Bifidobacterium as claimed in any of  claims 2  to  6  wherein the cells of the immune system are of gastrointestinal, respiratory or genitourinary origin.  
     
     
         9 . A strain of  Bifidobacterium longum infantis  isolated from resected and washed human gastrointestinal tract which is significantly immunomodulatory following oral consumption in humans.  
     
     
         10 . A strain of Bifidobacterium as claimed in any of  claims 1  to  9  which has significant anti-inflammatory effect following oral consumption in humans.  
     
     
         11 . A strain of Bifidobacterium isolated from resected and washed human gastrointestinal tract which is capable of combating the effects of inflammatory bowel disease, said capability being maintained in the presence of physiological concentrations of human bile and human gastric juice.  
     
     
         12 . A strain of  Bifidobacterium longum infantis  according to  claim 11 , wherein the capability of combating the effects of inflammatory bowel disease is measured by measuring a reversal of a wasting disease induced in severe combined immunodeficient recipient mice (SCID) which have been administered purified CD4 + , CD45RB high  T cells.  
     
     
         13 . A strain of Bifidobacterium as claimed in any preceding claim, which has inhibitory activity against a broad range of Gram positive and Gram negative bacteria.  
     
     
         14 . A strain of Bifidobacterium as claimed in preceding claim, wherein the strain exhibits a broad-spectrum of activity against bacteria including Staphylococcus, Pseudomonas, Coliform and Bacillus species.  
     
     
         15 . A strain of  Bifidobacterium longum infantis  UCC35624.  
     
     
         16 . A strain of  Bifidobacterium longum infantis  UCC35624 or mutant or variant thereof isolated from resected and washed human gastrointestinal tract which is significantly immunomodulatory following oral consumption in humans.  
     
     
         17 . A strain of  Bifidobacterium longum infantis  UCC35624 as claimed in  claim 16  wherein the mutant is a genetically modified mutant.  
     
     
         18 . A strain of  Bifidobacterium longum infantis  UCC35624 as claimed in  claim 16  wherein the variant is a naturally occurring variant of  Bifidobacterium longum infantis  UCC35624.  
     
     
         19 . A strain of Bifidobacterium as claimed in any of  claims 1  to  18  in the form of viable cells.  
     
     
         20 . A strain of Bifidobacterium as claimed in any of  claims 1  to  18  in the form of non-viable cells.  
     
     
         21 . An antimicrobial agent obtained from a strain of Bifidobacterium as claimed in any of  claims 1  to  20  which is antagonistic to the growth of other organisms.  
     
     
         22 . A formulation which comprises a strain of Bifidobacterium as claimed in any of  claims 1  to  20 .  
     
     
         23 . A formulation as claimed in  claim 22 , which comprises two or more strains of Bifidobacterium.  
     
     
         24 . A formulation as claimed in  claim 22  or  23 , which includes another probiotic material.  
     
     
         25 . A formulation as claimed in any of  claims 22  to  24 , which includes a prebiotic material.  
     
     
         26 . A formulation as claimed in any of  claims 22  to  25 , which includes a strain of  Lactobacillus salivarius.    
     
     
         27 . A formulation as claimed in  claim 26  wherein the strain of  Lactobacillus salivarius  is in the form of viable cells.  
     
     
         28 . A formulation as claimed in  claim 26  wherein the strain of  Lactobacillus salivarius  is in the form of non-viable cells.  
     
     
         29 . A formulation as claimed in any of  claims 26  to  28 , wherein the  Lactobacillus salivarius  is isolated from resected and washed human gastrointestinal tract, the  Lactobacillus salivarius  being significantly immunomodulatory following oral consumption in humans.  
     
     
         30 . A formulation as claimed in any of  claims 26  to  29 , wherein the strain of  Lactobacillus salivarius  is isolated from resected and washed human gastrointestinal tract which inhibits a broad range of Gram positive and Gram negative micro-organisms.  
     
     
         31 . A formulation as claimed in any of  claims 26  to  30  wherein the strain of  Lactobacillus salivarius  secretes a product having antimicrobial activity into a cell-free supernatant, said activity being produced only by growing cells and being destroyed by proteinase K and pronase E, the inhibitory properties of said strain and its secretory products being maintained in the presence of physiological concentration of human bile and human gastric juice.  
     
     
         32 . A formulation as claimed in any of  claims 26  to  31 , wherein the strain of  Lactobacillus salivarius  is  Lactobacillus salivarius  strain UCC 118 or a mutant or variant thereof.  
     
     
         33 . A formulation as claimed in  claim 32  wherein the mutant is a genetically modified mutant.  
     
     
         34 . A formulation as claimed in  claim 32  wherein the variant is a naturally occurring variant of  Lactobacillus salivarius.    
     
     
         35 . A formulation as claimed in any of  claims 22  to  34  which includes an ingestable carrier.  
     
     
         36 . A formulation as claimed in  claim 35  wherein the ingestable carrier is a pharmaceutically acceptable carrier such as a capsule, tablet or powder.  
     
     
         37 . A formulation as claimed in  claim 36  wherein the ingestable carrier is a food product such as acidified milk, yoghurt, frozen yoghurt, milk powder, milk concentrate, cheese spreads, dressings or beverages.  
     
     
         38 . A formulation as claimed in any of  claims 22  to  37  which further comprises a protein and/or peptide, in particular proteins and/or peptides that are rich in glutamine/glutamate, a lipid, a carbohydrate, a vitamin, mineral and/or trace element.  
     
     
         39 . A formulation as claimed in  claims 22  to  38  wherein the Bifidobacterium is present at more than 10 6  cfu per gram of delivery system.  
     
     
         40 . A formulation as claimed in  claims 22  to  39  which includes an adjuvant.  
     
     
         41 . A formulation as claimed in  claims 22  to  40  which includes a bacterial component.  
     
     
         42 . A formulation as claimed in  claims 22  to  41  which includes a drug entity.  
     
     
         43 . A formulation as claimed in  claims 22  to  42  which includes a biological compound.  
     
     
         44 . A formulation as claimed in  claims 22  to  43  for oral immunisation.  
     
     
         45 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in foodstuffs.  
     
     
         46 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use as a medicament.  
     
     
         47 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of undesirable inflammatory activity.  
     
     
         48 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of undesirable gastrointestinal inflammatory activity such as inflammatory bowel disease eg. Crohns disease or ulcerative colitis, irritable bowel syndrome; pouchitis; or post infection colitis.  
     
     
         49 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of gastrointestinal cancer(s).  
     
     
         50 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of systemic disease such as rheumatoid arthritis.  
     
     
         51 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of autoimmune disorders due to undesirable inflammatory activity.  
     
     
         52 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of cancer due to undesirable inflammatory activity.  
     
     
         53 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis of cancer.  
     
     
         54 . A strain of Bifidobacterium as claimed in any of  claims 1  to  20  or a formulation as claimed in any of  claims 22  to  44  for use in the prophylaxis and/or treatment of diarrhoeal disease due undesirable inflammatory activity, such as  Clostridium difficile  associated diarrhoea, Rotavirus associated diarrhoea or post infective diarrhoea.