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 inflammatory activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer.

55 - 129 . (canceled)  
     
     
         130 . A biologically pure culture of a strain of  Bifidobacterium  isolated from a resected and washed human gastrointestinal tract, wherein the strain of  Bifidobacterium  secretes a factor that antagonizes the activity of at least one pro-inflammatory cytokine.  
     
     
         131 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 130 , herein the pro-inflammatory cytokine is TNF-α.  
     
     
         132 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 130 , wherein the pro-inflammatory cytokine is IL-8.  
     
     
         133 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 130 , wherein the strain of  Bifidobacterium  is bile resistant and grows in the presence of physiologically relevant human bile.  
     
     
         134 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 130 , wherein the strain of  Bifidobacterium  is significantly immunomodulatory following oral consumption in humans, as evidenced by a decrease in systemic levels of at least one pro-inflammatory cytokine in humans.  
     
     
         135 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the pro-inflammatory cytokine is TNF-α.  
     
     
         136 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the pro-inflammatory cytokine is IL-8.  
     
     
         137 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the pro-inflammatory cytokine is sIL-6R.  
     
     
         138 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the pro-inflammatory cytokine is IFNγ.  
     
     
         139 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the immunomodulatory effect is an increase in an anti-inflammatory cytokine; a decrease in a pro-inflammatory cytokine; an increase in an anti-inflammatory cytokine and a decrease in a pro-inflammatory cytokine; or production of a high anti-inflammatory cytokine to pro-inflammatory cytokine ratio in the human following oral consumption.  
     
     
         140 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain inhibits the growth of Gram positive bacteria, Gram negative bacteria, or both.  
     
     
         141 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain inhibits the growth of  Staphylcoccus  spp.,  Pseudomonas  spp.,  Coliform  spp.,  Bacillus  spp., or a combination thereof.  
     
     
         142 . The biologically pure culture of a strain according to  claim 134 , wherein the strain of  Bifidobacterium  comprises  Bifidobacterium longum infantis.    
     
     
         143 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain is  Bifidobacterium longum infantis  UCC35624 or a mutant or a variant thereof.  
     
     
         144 . The biologically pure culture of a strain according to  claim 143 , wherein the strain of  Bifidobacterium  comprises  Bifidobacterium longum infantis  UCC35624.  
     
     
         145 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 143 , wherein the mutant is a genetically modified mutant.  
     
     
         146 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 143 , wherein the variant is a naturally occurring variant.  
     
     
         147 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain is in the form of viable cells.  
     
     
         148 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain is in the form of non-viable cells.  
     
     
         149 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain of  Bifidobacterium  is immunomodulatory to substantially the same extent as  Bifidobacterium longum infantis  UCC35624.  
     
     
         150 . A formulation comprising the biologically pure culture of a strain of  Bifidobacterium  isolated from a resected and washed human gastrointestinal tract, wherein the strain of  Bifidobacterium  secretes a factor that antagonizes the activity of at least one pro-inflammatory cytokine.  
     
     
         151 . The formulation of  claim 150  comprising two or more strains of  Bifidobacterium.    
     
     
         152 . The formulation of  claim 150 , wherein the strain of  Bifidobacterium  is significantly immunomodulatory following oral consumption in humans, as evidenced by a decrease in systemic levels of at least one pro-inflammatory cytokine in humans.  
     
     
         153 . The formulation of  claim 150 , further comprising an additional probiotic material or a prebiotic material.  
     
     
         154 . The formulation of  claim 150 , further comprising a strain of  Lactobacillus salivarius.    
     
     
         155 . The formulation of  claim 154 , wherein the strain of  Lactobacillus salivarius  is in the form of viable cells.  
     
     
         156 . The formulation of  claim 154 , wherein the strain of  Lactobacillus salivarius  is in the form of non-viable cells.  
     
     
         157 . The formulation of  claim 154 , wherein the strain of  Lactobacillus salivarius  is isolated from a resected and washed human gastrointestinal tract and is significantly immunomodulatory following oral consumption in humans.  
     
     
         158 . The formulation of  claim 154 , wherein the strain of  Lactobacillus salivarius  inhibits the growth of Gram positive bacteria, Gram negative bacteria, or both.  
     
     
         159 . The formulation of  claim 154 , wherein the strain of  Lactobacillus salivarius  is  Lactobacillus salivarius  strain UCC 118 or a mutant or a variant thereof.  
     
     
         160 . The formulation of  claim 159 , wherein the mutant is a genetically modified mutant.  
     
     
         161 . The formulation of  claim 159 , wherein the variant is a naturally occurring variant.  
     
     
         162 . The formulation of  claim 150 , further comprising an ingestible carrier.  
     
     
         163 . The formulation of  claim 162 , wherein the ingestible carrier is a pharmaceutically acceptable carrier.  
     
     
         164 . The formulation of  claim 163 , wherein the pharmaceutically acceptable carrier is in the form of a capsule, a tablet, or a powder.  
     
     
         165 . The formulation of  claim 162 , wherein the ingestible carrier is a food product.  
     
     
         166 . The formulation of  claim 165 , wherein the food product is acidified milk, a yogurt, a frozen yogurt, a milk powder, a milk concentrate, a cheese spread, a dressing, or a beverage.  
     
     
         167 . The formulation of  claim 150 , further comprising a protein, a peptide, a lipid, a carbohydrate, a vitamin, a mineral, or a trace element.  
     
     
         168 . The formulation of  claim 167 , wherein the protein or the peptide is rich in glutamine, glutamate, or both.  
     
     
         169 . The formulation of  claim 150 , wherein the  Bifidobacterium  is present at more than 10 6  cfu per gram of the formulation.  
     
     
         170 . The formulation of  claim 150 , further comprising an adjuvant.  
     
     
         171 . The formulation of  claim 150 , further comprising a bacterial component.  
     
     
         172 . The formulation of  claim 150 , further comprising a drug entity.  
     
     
         173 . The formulation of  claim 150 , further comprising a biological compound.  
     
     
         174 . The formulation of  claim 150 , wherein the formulation is suitable for oral administration to a subject.  
     
     
         175 . A foodstuff comprising the strain of  Bifidobacterium  of  claim 134 .  
     
     
         176 . A foodstuff comprising the formulation of  claim 150 .  
     
     
         177 . A pharmaceutical composition comprising the  Bifidobacterium  strain of  claim 134  and a pharmaceutically acceptable carrier.  
     
     
         178 . A pharmaceutical composition comprising the formulation of  claim 150  and a pharmaceutically acceptable carrier.  
     
     
         179 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 134 , wherein the strain is capable of reducing or inhibiting the effects of inflammatory bowel disease in the presence of physiological concentrations of human bile and human gastric juice.  
     
     
         180 . The biologically pure culture of a strain of  Bifidobacterium  according to  claim 179 , wherein the strain is capable of reducing or inhibiting the effects of inflammatory bowel disease in the presence of physiological concentrations of human bile and human gastric juice, as evidenced by measuring a reversal of wasting disease induced in severe combined immunodeficient recipient mice (SCID) which have been administered purified CD4 + , CD45RB high  T cells.  
     
     
         181 . The formulation of  claim 150 , wherein the formulation is capable of reducing or inhibiting the effects of inflammatory bowel disease in the presence of physiological concentrations of human bile and human gastric juice.  
     
     
         182 . The formulation of  claim 181 , wherein the formulation is capable of reducing or inhibiting the effects of inflammatory bowel disease in the presence of physiological concentrations of human bile and human gastric juice, as evidenced by measuring a reversal of wasting disease induced in severe combined immunodeficient recipient mice (SCID) which have been administered purified CD4 + , CD45RB high  T cells.