TY - JOUR

T1 - Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans

T2 - A Randomized Double-Blind Placebo-Controlled Trial

AU - Reijnders, Dorien

AU - Goossens, Gijs H

AU - Hermes, Gerben D A

AU - Neis, Evelien P J G

AU - van der Beek, Christina M

AU - Most, Jasper

AU - Holst, Jens J

AU - Lenaerts, Kaatje

AU - Kootte, Ruud S

AU - Nieuwdorp, Max

AU - Groen, Albert K

AU - Olde Damink, Steven W M

AU - Boekschoten, Mark V

AU - Smidt, Hauke

AU - Zoetendal, Erwin G

AU - Dejong, Cornelis H C

AU - Blaak, Ellen E

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.cmet.2016.06.016

DO - 10.1016/j.cmet.2016.06.016

M3 - Journal article

C2 - 27411009

VL - 24

SP - 63

EP - 74

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -