Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.

BACKGROUND: Obesity has been associated with changes in the composition function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, hypothesized that short term administration of oral antibiotics in affect fecal microbiota composition and subsequently bile acid and metabolism. METHODS: In this single blinded randomized controlled trial, obese subjects with metabolic syndrome were randomized to 7 days of 500mg t.i.d. or 7 days of vancomycin 500mg t.i.d. At baseline and after therapy, fecal microbiota composition (Human Intestinal Tract Chip microarray), fecal and plasma bile acid concentrations as well as sensitivity (hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose were measured. RESULTS: Vancomycin reduced fecal microbial diversity decrease of gram-positive bacteria (mainly Firmicutes) and a increase in gram-negative bacteria (mainly Proteobacteria). vancomycin decreased fecal secondary bile acids with a simultaneous increase in primary bile acids in plasma (p<0.05). Moreover, changes in bile acid concentrations were predominantly associated with altered Finally, administration of vancomycin decreased peripheral insulin (p<0.05). Amoxicillin did not affect any of these parameters. administration of vancomycin significantly impacts host physiology by intestinal microbiota diversity, bile acid dehydroxylation and sensitivity in subjects with metabolic syndrome. These data show that microbiota, particularly of the Firmicutes phylum contributes to bile glucose metabolism in humans. This trial is registered at the Dutch Register (NTR2566)