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. [Display omitted] •Vancomycin but not amoxicillin treatment alters human gut microbiota composition•Vancomycin treatment alters short-chain fatty acid and bile acid concentrations•Modulation of adult microbiota by 7-day antibiotics does not affect host metabolism•Host metabolism remained unchanged at 8-week follow-up, despite deviant microbiota Reijnders et al. show that a 7-day antibiotic treatment (amoxicillin/vancomycin) has no clinically relevant impact on host metabolism in obese humans, both directly after treatment cessation and at 8-week follow-up, despite profound changes in gut microbiota, short-chain fatty acid, and bile acid concentrations induced by vancomycin.