title: Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.
abstract: The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands; Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands.
authors.forename: Dorien
authors.initials: D
authors.lastname: Reijnders
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands; Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands.
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Goossens
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, 6703HB Wageningen, The Netherlands.
authors.forename: Gerben D A
authors.initials: GD
authors.lastname: Hermes
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands.
authors.forename: Evelien P J G
authors.initials: EP
authors.lastname: Neis
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands.
authors.forename: Christina M
authors.initials: CM
authors.lastname: van der Beek
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Most
authors.affiliation: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands.
authors.forename: Kaatje
authors.initials: K
authors.lastname: Lenaerts
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Vascular Medicine and Department of Internal Medicine, University of Amsterdam, 1100DD Amsterdam, The Netherlands.
authors.forename: Ruud S
authors.initials: RS
authors.lastname: Kootte
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Vascular Medicine and Department of Internal Medicine, University of Amsterdam, 1100DD Amsterdam, The Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Nieuwdorp
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University Medical Center Groningen, 9713GZ Groningen, The Netherlands.
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands; Department of HPB Surgery and Liver Transplantation, Institute of Liver and Digestive Health, University College London, London, United Kingdom.
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, 6700EV Wageningen, The Netherlands.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, 6703HB Wageningen, The Netherlands.
authors.forename: Hauke
authors.initials: H
authors.lastname: Smidt
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, 6703HB Wageningen, The Netherlands.
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Zoetendal
authors.affiliation: Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands.
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229ER Maastricht, The Netherlands; Top Institute Food and Nutrition, 6700AN Wageningen, The Netherlands. Electronic address: e.blaak@maastrichtuniversity.nl.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D020148:Butyric Acid / Q000097:blood; D048430:Cell Shape / Q000187:drug effects; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D009928:Organ Specificity / Q000187:drug effects; D010539:Permeability; D010919:Placebos; D013379:Substrate Specificity / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D007328:Insulin; D010919:Placebos; D020148:Butyric Acid; D014640:Vancomycin; D000658:Amoxicillin