Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: a Randomized Double-blind Placebo-controlled Trial

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.

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Reijnders D, Goossens GH, Hermes GD, Neis EP, van der Beek CM, Most J, Holst JJ, Lenaerts K, Kootte RS, Nieuwdorp M, Groen AK, Olde Damink SW, Boekschoten MV, Smidt H, Zoetendal EG, Dejong CH, Blaak EE