Lipoteichoic acid from lactic acid bacteria and its use to modulate immune responses mediated by gram-negative, potential pathogenic gram-positive bacteria

Abstract

The invention relates to a composition for modulating the immune responses induced by Gram negative bacteria, potential pathogenic Gram positive bacteria and/or their derivatives, comprising lipoteichoic acid from lactic acid bacteria as an active ingredient. It also relates to the use of a lipoteichoic acid from lactic acid bacteria as an active ingredient and/or lactic acid bacteria producing it and/or its supernatant of culture, in the manufacture of a medicament, an oral or topical product for cosmetic, dermatological or ophtalmological applications, a food or petfood compostiion for modulating bacterial colonisation, immune responses and decreasing the inflammatory processes associated with bacterially-mediated disease and infection in the gastrointestinal tract, bone, skin, eye, ear, lung and oral cavity. The invention also relates to lipoteichoic acid selected thereof.

1 . A composition for modulating the immune responses induced by Gram negative bacteria, potential pathogenic Gram positive bacteria and/or their derivatives, comprising lipoteichoic acid from lactic acid bacteria as an active ingredient.  
     
     
         2 . A composition according to claims  1 , which is particularly intended for modulating immune responses involved during bacterial colonisation or infection and/or preventing or reducing inflammatory processes induced thereby, in the gastrointestinal tract, bone, eye, lung, ear and oral cavity in humans or animals.  
     
     
         3 . A composition according to  claim 1  or  2 , wherein the lipoteichoic acid from lactic acid bacteria has been selected for its ability to bind to CD14 and for their inability to induce the release of proinflammatory cytokines such as IL-8 or TNF-alpha from intestinal epithelial cells.  
     
     
         4 . A composition according to any of  claims 1  to  3 , wherein the lipoteichoic acid is from lactic acid bacteria belonging to the genus Lactobacillus, Bifidobacterium or Steptococcocus, preferably from the group consisting of  Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus helveticus, Lactobacillus casei, Lactobacillus plantarum, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium animalis, Streptococcus thermophilus.    
     
     
         5 . A composition according to one of  claims 1  to  4 , wherein the lactic acid bacteria is  Lactobacillus johnsonii  CNCM I-1225,  Lactobacillus acidophilus CNCM I- 2332.  
     
     
         6 . A composition according to one of  claims 1  to  5 , which contains lactic acid bacteria producing said lipoteichoic acid or a supernatant of its culture.  
     
     
         7 . A composition according to any of  claims 1  to  6 , wherein the lipoteichoic acid is present in an amount which corresponds to an amount of bacteria varying from 10 5  cfu/g to about 10 11  cfu/g in a food composition to about 10 5  cfu/g to 10 16  cfu/g in a pharmaceutical preparation.  
     
     
         8 . A composition according to any of  claims 1  to  7 , which is in the form of a medicament, an oral or topical product for cosmetic, dermatological or ophtalmological applications, a food or pet food composition.  
     
     
         9 . A lipoteichoic acid from lactic acid bacteria that is able to bind to CD14 and unable to induce the release of proinflammatory cytokines such as IL-8 or TNF-alpha from intestinal epithelial cells.  
     
     
         10 . A lipoteichoic acid according to  claim 9 , which contains its lipid moiety.  
     
     
         11 . A lipoteichoic acid according to  claim 9  or  10 , from lactic acid bacteria belonging to the genus Lactobacillus, Bifidobacterium or Steptococcocus.  
     
     
         12 . A lipoteichoic acid according to one of  claims 9  to  11 , wherein the lactic acid bacteria is selected from the group consisting of  Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus helveticus, Lactobacillus casei, Lactobacillus plantarum, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium animalis  or  Streptococcus thermophilus.    
     
     
         13 . A lipoteichoic acid according to one of  claims 9  to  12 , wherein the lactic acid bacteria is  Lactobacillus johnsonii  CNCM I-1225 or  Lactobacillus acidophilus  CNCM I-2332.  
     
     
         14 . Use of at least one lipoteichoic acid from lactic acid bacteria and/or lactic acid bacteria producing it and/or its supernatant of culture, for the preparation of a composition intended for modulating the immune responses induced by Gram negative bacteria, potential pathogenic Gram positive bacteria and/or their derivatives in a human or an animal.  
     
     
         15 . Use of a lipoteichoic acid according to one of  claims 9  to  13 .  
     
     
         16 . Use according to  claim 14  or  15 , for reducing or preventing inflammatory processes associated with bacterially-mediated disease or LTA/LPS-mediated disorders in the gastrointestinal tract, bone, skin, eye, ear, lung and oral cavity in humans or animals.  
     
     
         17 . Use according to any of  claims 14  to  16 , in food -compositions or enteral feeds, for infant nutrition, pet nutrition and animal feeds, for clinical nutrition or for pharmaceutical applications.  
     
     
         18 . Use according to any of  claims 14  to  17 , in cosmetic or dermatological applications in the form of topical or oral preparations, ophthalmic applications, or oral applications.  
     
     
         19 . A method of modulating the immune responses induced by Gram negative bacteria, potential pathogenic Gram positive bacteria and/or their derivatives in a human or an animal, which comprises administering the human or animal, an effective amount of a lipoteichoic acid from lactic acid bacteria and/or lactic acid bacteria producing it and/or its supernatant of culture, or composition comprising a lipoteichoic acid from lactic acid bacteria as the active ingredient and/or lactic acid bacteria producing it and/or its supernatant of culture,.  
     
     
         20 . A method for reducing or preventing inflammatory processes associated with bacterially-mediated disease or LTA/LPS-mediated disorders in the gastrointestinal tract, bone, skin, eye, ear, lung and oral cavity in humans or animals, which comprises administering the human or animal, an effective amount of a lipoteichoic acid from lactic acid bacteria and/or lactic acid bacteria producing it and/or its supernatant of culture, or composition comprising a lipoteichoic acid from lactic acid bacteria as the active ingredient and/or lactic acid bacteria producing it and/or its supernatant of culture,.  
     
     
         21 . A method according to  claim 19  or  20 , in which the composition is according to  claim 1  to  8 .  
     
     
         22 . A method of modulating an immune response induced in a pet animal by Gram negative bacteria, potential pathogenic Gram positive bacteria and/or their derivatives, the method including administering a pet animal a composition containing a moiety of a probiotic bacterial strain capable of modulating such response.  
     
     
         23 . Amethod according to  claim 22 , which includes administering a pet animal a composition containing a probiotic micro-organism, its supernatant of culture or a metabolite thereof, the said probiotic etc being capable of at least transiently adhering to the intestinal epithelium of the pet animal.  
     
     
         24 . A method according to  claim 22  or  23 , which includes administering the composition as a component of a nutritionally balanced meal. In a preferred embodiment, the component is included in a wet or dry pet food formulation.  
     
     
         25 . A pet food formulation comprising a nutritionally balanced meal and an active ingredient selected for its capacity to modulate an immune response induced in a pet animal by a Gram negative bacterial strain, potential pathogenic Gram positive bacterial strain and/or a derivative thereof.