Method of Treating Lactose Intolerance Using Genetically Engineered Bacteria

Abstract

The present invention relates to genetically engineered bacteria that are able to colonize the mammalian intestine and actively produce mammalian lactase (lactose-phlorizin hydrolase or LPH). This lactose-digesting enzyme is stable and active under the conditions normally found in the mammalian small intestine. Experimental subjects colonized with the genetically engineered bacteria show improved ability to digest lactose in dairy foods.

1 . A composition for treating lactose intolerance in a mammal, comprising  Lactobacillus acidophilus  bacteria that are genetically modified to express a mammalian lactase-phlorizin hydrolase enzyme under the control of a CMV promoter. 
     
     
         2 . The composition of  claim 1 , wherein said bacteria are capable of adhering to the intestinal surface. 
     
     
         3 . The composition of  claim 2 , wherein said intestinal surface is within the small intestine. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein said bacteria are present as a live suspension. 
     
     
         8 . The composition of  claim 1 , wherein said bacteria are present as a lyophilized powder. 
     
     
         9 . The composition of  claim 8 , further comprising an acid resistant coating. 
     
     
         10 . The composition of  claim 1 , wherein said mammalian lactase-phlorizin hydrolase is expressed only the presence of lactose. 
     
     
         11 . A method of treating lactose intolerance in a mammal, comprising contacting the intestinal surface of said mammal with  Lactobacillus acidophilus  bacteria that are genetically modified to express a mammalian lactase-phlorizin hydrolase enzyme under the control of a CMV promoter. 
     
     
         12 . The method of  claim 11 , wherein the intestinal surface is within the small intestine. 
     
     
         13 .- 15 . (canceled) 
     
     
         16 . The method of  claim 11 , wherein the contacting step involves oral administration of said bacteria. 
     
     
         17 . The method of  claim 11 , wherein said bacteria are coated with acid resistant coating. 
     
     
         18 . The method of  claim 16 , further comprising a step of reducing the acidity of the stomach environment of said mammal prior to said oral administration of bacteria. 
     
     
         19 . The method of  claim 16 , further comprising a step of treating said mammal with antibiotics prior to said oral administration of bacteria. 
     
     
         20 . A method of preparing a composition for treating lactose intolerance in a mammal, comprising genetically modifying bacteria to express lactase-phlorizin hydrolase enzyme under the control of a CMV promoter. 
     
     
         21 . The method of  claim 20 , wherein said bacteria belong to the group homolactic Lactic Acid Bacteria. 
     
     
         22 . The method of  claim 21 , wherein said bacteria are selected from a group consisting of  Lactobacillus acidophilus, Lactobacillus delbruekii  subsp.  bulgaricus, Bifidobacterium lactis  and  Streptococcus thermophilus.