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

Anne Vrieze, Carolien Out, Susana Fuentes, Lisanne Jonker, Isaie Reuling, Ruud S Kootte, Els van Nood, Frits Holleman, Max Knaapen, Johannes A Romijn, Maarten R Soeters, Ellen E Blaak, Geesje M Dallinga-Thie, Dorien Reijnders, Mariëtte T Ackermans, Mireille J Serlie, Filip K Knop, Jenst J Holst, Claude van der Ley, Ido P KemaErwin G Zoetendal, Willem M de Vos, Joost B L Hoekstra, Erik S Stroes, Albert K Groen, Max Nieuwdorp

Research output: Contribution to journalArticleAcademicpeer-review

374 Citations (Scopus)


BACKGROUND & AIMS: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism.

METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured.

RESULTS: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters.

CONCLUSIONS: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566).

Original languageEnglish
Pages (from-to)824-831
Number of pages8
JournalJournal of Hepatology
Issue number4
Publication statusPublished - Apr 2014
Externally publishedYes

Bibliographical note

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


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