Anne Vrieze1, Carolien Out2, Susana Fuentes3, Lisanne Jonker1, Isaie Reuling1, Ruud S Kootte4, Els van Nood1, Frits Holleman1, Max Knaapen4, Johannes A Romijn1, Maarten R Soeters5, Ellen E Blaak6, Geesje M Dallinga-Thie4, Dorien Reijnders6, Mariëtte T Ackermans7, Mireille J Serlie5, Filip K Knop8, Jenst J Holst9, Claude van der Ley10, Ido P Kema10, Erwin G Zoetendal3, Willem M de Vos11, Joost B L Hoekstra1, Erik S Stroes4, Albert K Groen2, Max Nieuwdorp12. 1. Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands. 2. Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands. 4. Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. 5. Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands. 6. Department of Human Metabolism, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands. 7. Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands. 8. Department of Internal Medicine, Gentofte Hospital, Hellerup, Denmark; NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Denmark. 9. NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Denmark. 10. Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands. 11. Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands; Department of Basic Veterinary Medicine, University of Helsinki, Helsinki, Finland. 12. Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: m.nieuwdorp@amc.uva.nl.
Abstract
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).
RCT Entities:
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).
Authors: Paula Roca-Saavedra; Veronica Mendez-Vilabrille; Jose Manuel Miranda; Carolina Nebot; Alejandra Cardelle-Cobas; Carlos M Franco; Alberto Cepeda Journal: J Physiol Biochem Date: 2017-05-09 Impact factor: 4.158
Authors: K W ter Horst; P W Gilijamse; K E Koopman; B A de Weijer; M Brands; R S Kootte; J A Romijn; M T Ackermans; M Nieuwdorp; M R Soeters; M J Serlie Journal: Int J Obes (Lond) Date: 2015-07-09 Impact factor: 5.095