title: Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.
abstract: OBJECTIVE
  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: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Anne
authors: A
authors: Vrieze
authors: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Carolien
authors: C
authors: Out
authors: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors: Susana
authors: S
authors: Fuentes
authors: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Lisanne
authors: L
authors: Jonker
authors: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Isaie
authors: I
authors: Reuling
authors: Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Ruud S
authors: RS
authors: Kootte
authors: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Els
authors: E
authors: van Nood
authors: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Frits
authors: F
authors: Holleman
authors: Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Max
authors: M
authors: Knaapen
authors: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Johannes A
authors: JA
authors: Romijn
authors: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors: Maarten R
authors: MR
authors: Soeters
authors: Department of Human Metabolism, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands.
authors: Ellen E
authors: EE
authors: Blaak
authors: Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Geesje M
authors: GM
authors: Dallinga-Thie
authors: Department of Human Metabolism, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht University, The Netherlands.
authors: Dorien
authors: D
authors: Reijnders
authors: Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Mariëtte T
authors: MT
authors: Ackermans
authors: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors: Mireille J
authors: MJ
authors: Serlie
authors: 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.
authors: Filip K
authors: FK
authors: Knop
authors: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Denmark.
authors: Jenst J
authors: JJ
authors: Holst
authors: Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors: Claude
authors: C
authors: van der Ley
authors: Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors: Ido P
authors: IP
authors: Kema
authors: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors: Erwin G
authors: EG
authors: Zoetendal
authors: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands; Department of Basic Veterinary Medicine, University of Helsinki, Helsinki, Finland.
authors: Willem M
authors: WM
authors: de Vos
authors: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Joost B L
authors: JB
authors: Hoekstra
authors: Department of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Erik S
authors: ES
authors: Stroes
authors: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Albert K
authors: AK
authors: Groen
authors: 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.
authors: Max
authors: M
authors: Nieuwdorp
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D064307:Microbiota / Q000187:drug effects*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D016037:Single-Blind Method; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D014640:Vancomycin; D005947:Glucose
keywords: Amoxicillin; Antibiotics; Bile acids; Insulin resistance; Intestinal microbiota; Metabolic syndrome; Vancomycin