Production and use of bacterial histamine

Abstract

A method is provided of selecting specific probiotic lactic acid bacteria producing histamine and the use of such strains for beneficial effects for mammals. The method includes selecting a lactic acid bacterial strain for use in the local production of histamine in a mammal, and further comprises screening bacteria for the presence of an. active histidine operon and selecting a strain which has an active histidine operon and is capable of producing histamine. Preferably said strain is selected for its ability to produce histamine at a level of greater than 250 pg/ml. The present invention further provides products comprising the strains obtainable by the selection methods of the invention for use in the local production, of histamine in a mammal, in particular for use in the treatment or prophylaxis of inflammatory conditions.

1 . A method of selecting a lactic acid bacterial strain for use in the local production of histamine in a mammal, wherein said method comprises screening bacteria for the presence of an active histidine operon and selecting a lactic acid bacterial strain which has an active histidine operon and is capable of producing histamine. 
     
     
         2 . The method of  claim 1 , wherein said lactic acid bacterial strain is a strain of  Lactobacillus reuteri.    
     
     
         3 . The method of  claim 1 , further comprising selecting said lactic acid bacterial strain for its ability to produce histamine at a level of greater than 300 ng/ml. 
     
     
         4 . The method of  claim 2 , wherein said lactic acid bacterial strain is a strain of  Lactobacillus reuteri.    
     
     
         5 . A method of treatment and/or prophylaxis of an inflammatory condition, comprising providing a lactic acid bacterial strain having an active histidine operon and capable of producing histamine. 
     
     
         6 . The method of  claim 5 , wherein the inflammatory condition is selected from the group consisting of colitis, inflammatory bowel disease, irritable bowel syndrome, diverticulosis, gingivitis and vaginitis. 
     
     
         7 . The method of  claim 5 , further comprising the administration of at least one further therapeutic or nutritional agent to the mammal. 
     
     
         8 . The method of  claim 7 , wherein said further therapeutic or nutritional agent comprises histidine or a histidine analog, an appropriate carbon source which supports the production of histamine by said strain, or a combination thereof. 
     
     
         9 . The method of  claim 8 , wherein the histidine or histidine analog is in the form of a histidine or histidine analog contained in a foodstuff or a food supplement. 
     
     
         10 . The method of  claim 8 , wherein the carbon source comprises glucose. 
     
     
         11 . A product for use in the local production of histamine in a mammal comprising cells of a lactic acid bacterial strain obtained by the selection method according to  claim 1 , wherein said lactic acid bacterial strain has an active histidine operon and is capable of producing histamine. 
     
     
         12 . The product of  claim 11 , wherein the local production of histamine is in the GI tract, GU tract, oral cavity, lungs, airways, or on the skin of said mammal. 
     
     
         13 . The product of  claim 11 , wherein said mammal is a human. 
     
     
         14 . The product of  claim 11 , wherein said lactic acid bacterial strain is a strain of  Lactobacillus reuteri.    
     
     
         15 . The product of  claim 13 , wherein the local production of histamine is in the GI tract, GU tract, oral cavity, lungs, airways, or on the skin of said mammal. 
     
     
         16 . The product of  claim 13 , wherein said lactic acid bacterial strain is a strain of  Lactobacillus reuteri.    
     
     
         17 . The product of  claim 11 , wherein said lactic acid bacterial strain is  Lactobacillus reuteri  6475. 
     
     
         18 . The product of  claim 11 , further comprising at least one additional component selected from the group consisting of an appropriate carbon source which supports the production of histamine by said strain, a source of histidine or histidine analog, and a combination thereof. 
     
     
         19 . The product of  claim 18 , wherein said histidine or histidine analog is in the form of a histidine or histidine analog contained in a foodstuff or a food supplement. 
     
     
         20 . The product of  claim 18 , wherein said carbon source comprises glucose.