Tungstate treatment of the dysbiosis associated with gastrointestinal inflammation

Abstract

The present invention provides compositions of therapeutic agents and methods of use for reducing and/or treating gastrointestinal inflammation. In particular aspects, the tungstate salts described herein and pharmaceutical compositions thereof inhibit the activity of one or a plurality of anaerobic respiratory enzymes in facultative anaerobic bacteria such as, for example, Enterobacteriaceae, that can exacerbate inflammation. In particular embodiments, the present invention provides compositions of therapeutic agents for treating gastrointestinal inflammation, as well as methods for treating or preventing gut microbial imbalance due to an increase in the abundance of intestinal Enterobacteriaceae.

1 . A method for treating dysbiosis in a subject having gastrointestinal inflammation, the method comprising administering to the subject a therapeutically effective amount of a tungstate salt. 
     
     
         2 . The method of  claim 1 , wherein the gastrointestinal inflammation comprises inflammatory bowel disease (IBD). 
     
     
         3 . The method of  claim 2 , wherein the IBD comprises ulcerative colitis (UC), Crohn's disease (CD), or indeterminate colitis (IC). 
     
     
         4 . The method of  claim 1 , wherein the gastrointestinal inflammation comprises colitis. 
     
     
         5 . The method of  claim 1 , wherein the gastrointestinal inflammation comprises HIV enteropathy. 
     
     
         6 . The method of  claim 1 , wherein an increased amount of Enterobacteriaceae is present in the subject's gastrointestinal tract. 
     
     
         7 . The method of  claim 1 , wherein the tungstate salt is selected from the group consisting of sodium tungstate, potassium tungstate, magnesium tungstate, calcium tungstate, and mixtures thereof. 
     
     
         8 . The method of  claim 1 , wherein the therapeutically effective amount is substantially equivalent to about 100 mg twice daily for about 6 weeks. 
     
     
         9 . The method of  claim 1 , wherein the tungstate salt is administered orally. 
     
     
         10 . A method for preventing dysbiosis in a subject having or suspected of having gastrointestinal inflammation, the method comprising administering to the subject a therapeutically effective amount of a tungstate salt. 
     
     
         11 . The method of  claim 10 , wherein the subject does not have symptoms of inflammation-associated dysbiosis. 
     
     
         12 . The method of  claim 10 , wherein the gastrointestinal inflammation comprises inflammatory bowel disease (IBD). 
     
     
         13 . The method of  claim 12 , wherein the IBD comprises ulcerative colitis (UC), Crohn's disease (CD), or indeterminate colitis (IC). 
     
     
         14 . The method of  claim 10 , wherein the gastrointestinal inflammation comprises colitis. 
     
     
         15 . The method of  claim 10 , wherein the gastrointestinal inflammation comprises HIV enteropathy. 
     
     
         16 . The method of  claim 10 , wherein the tungstate salt is selected from the group consisting of sodium tungstate, potassium tungstate, magnesium tungstate, calcium tungstate, and mixtures thereof. 
     
     
         17 . The method of  claim 10 , wherein the tungstate salt is administered orally. 
     
     
         18 - 50 . (canceled)