Vrieze, Anne3; Out, Carolien4; Fuentes, Susana5; Jonker, Lisanne3; Reuling, Isaie3; Kootte, Ruud S3; van Nood, Els3; Holleman, Frits3; Knaapen, Max3; Romijn, Johannes A3; Soeters, Maarten R6; Blaak, Ellen E7; Dallinga-Thie, Geesje M3; Reijnders, Dorien7; Ackermans, Mariëtte T8; Serlie, Mireille J6; Knop, Filip K12; Holst, Jens Juul13; van der Ley, Claude11; Kema, Ido P11; Zoetendal, Erwin G5; de Vos, Willem M5; Hoekstra, Joost B L3; Stroes, Erik S3; Groen, Albert K4; Nieuwdorp, Max3
1 Section of Endocrinology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.4 Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.5 Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.6 Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.7 Department of Human Metabolism, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands.8 Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands.9 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet10 Section for Translational Metabolic Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet11 Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.12 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet13 Section for Translational Metabolic Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
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).
Journal of Hepatology, 2014, Vol 60, Issue 4, p. 824-31