ena-STUDY-UT SOUTHWESTERN MEDICAL CENTER-24-01-2017-21:38:30:502-51
Female 9-12 week old C57BL/6J wild-type mice were obtained from the Jackson Laboratory (Bar Harbor) or Charles River Laboratory (Morrisville), as indicated. Mice were randomly assigned into cages before the experiment. The drinking water was replaced with either filter-sterilized water (mock-treatment), or a filter-sterilized solution of 0.2% (w/v) sodium tungstate (Sigma, St Louis), or a filter-sterilized solution of 2% or 3% (w/v) dextran sulfate sodium (DSS; relative molecular mass 36,000 – 50,000; MP Biomedicals) in water at the indicated concentrations, or a filter-sterilized solution of DSS and 0.2% (w/v) sodium tungstate.
Inflammatory diseases afflicting the gastrointestinal tract are invariably associated with a concomitant disruption of gut microbial communities. A common feature of dysbiosis is an expansion of facultative anaerobic bacteria of the Enterobacteriaceae family (phylum Proteobacteria), which has been reported in numerous human diseases as well as animal models of gut inflammation (1-8). Here we show that tungstate treatment selectively inhibits molybdenum cofactor-dependent microbial metabolic pathways that are only operational during episodes of inflammation. Oral tungstate treatment prevented an uncontrolled expansion of Enterobacteriaceae in murine models of colitis while no overt changes in the microbiota composition were noted under homeostatic conditions. Editing of microbiota composition through tungsten treatment reduced severity of intestinal inflammation. We conclude that a precision editing of the microbiota composition by tungstate treatment ameliorates the adverse effects of dysbiosis in the setting of gut inflammation.
Inflammatory diseases afflicting the gastrointestinal tract are invariably associated with a concomitant disruption of gut microbial communities. A common feature of dysbiosis is an expansion of facultative anaerobic bacteria of the Enterobacteriaceae family (phylum Proteobacteria), which has been reported in numerous human diseases as well as animal models of gut inflammation (1-8). Here we show that tungstate treatment selectively inhibits molybdenum cofactor-dependent microbial metabolic pathways that are only operational during episodes of inflammation. Oral tungstate treatment prevented an uncontrolled expansion of Enterobacteriaceae in murine models of colitis while no overt changes in the microbiota composition were noted under homeostatic conditions. Editing of microbiota composition through tungsten treatment reduced severity of intestinal inflammation. We conclude that a precision editing of the microbiota composition by tungstate treatment ameliorates the adverse effects of dysbiosis in the setting of gut inflammation.