Short-Term Microbiota Manipulation and Forearm Substrate Metabolism in Obese Men: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Objective: To investigate the impact of gut microbiota manipulation on fasting and postprandial skeletal muscle metabolism in humans.

Methods: 40 obese, insulin-resistant males were randomized to amoxicillin (broad-spectrum antibiotic), vancomycin (narrow-spectrum antibiotic), or placebo (7 days, 1,500 mg/day). Before and after treatment, forearm blood flow and metabolite fluxes across forearm muscle were measured under fasting and postprandial (high-fat mixed-meal) conditions.

Results: Vancomycin decreased bacterial diversity, reduced the abundance of Gram-positive Firmicutes, and increased the abundance of Gram-negative Proteobacteria, whereas amoxicillin did not affect microbial composition. Neither vancomycin nor amoxicillin treatment affected fasting and postprandial plasma glucose, free fatty acid (FFA), triacylglycerol (TAG), glycerol, lactate, and insulin concentrations or forearm blood flow. Fasting and postprandial net forearm muscle glucose uptake and the release of lactate were not significantly altered by antibiotic treatment as compared to placebo. Finally, antibiotic treatment did not change fasting and postprandial glycerol, FFA, and TAG fluxes across forearm muscle.

Conclusion: The present study demonstrates that short-term antibiotic treatment has no effects on fasting and postprandial forearm substrate metabolism and blood flow in obese men with impaired glucose metabolism. These data suggest that short-term strategies targeting the gut microbiota to improve metabolic health may not be effective in obese humans.

Trial registration: ClinicalTrials.gov NCT02241421.

Keywords: Antibiotics; Insulin resistance; Microbiota; Obesity; Skeletal muscle.

© 2018 The Author(s) Published by S. Karger GmbH, Freiburg.

Figures

Fig. 1

Effect of 7 days placebo (PLA) or VANCO treatment on plasma concentrations and fluxes of glucose, lactate, FFA, TAG and insulin across forearm muscle. Fasting (t = 0) and postprandial concentrations of (A) arterialized insulin, (B) glucose, (C) lactate, (D) free fatty acid (FFA) and (E) triacylglycerol (TAG) concentrations were not affected by VANCO as assessed by repeated measures ANOVA. VANCO did not affect forearm blood flow (F) and net fluxes of (G) glucose, (H) lactate, (I) FFA, and (J) TAG across forearm muscle are shown. A positive flux indicates net uptake across the forearm muscle whereas a negative flux indicates net release. Values are given as mean ± SEM (n = 37).

Fig. 2

Effect of 7 days placebo (PLA) or AMOX treatment on plasma concentrations and fluxes of glucose, lactate, FFA, TAG and insulin across forearm muscle. Fasting (t = 0) and postprandial concentrations of (A) arterialized insulin, (B) glucose, (C) lactate, (D) free fatty acid (FFA) and (E) triacylglycerol (TAG) concentrations were not affected by AMOX as assessed by repeated measures ANOVA. AMOX did not affect forearm blood flow (F) and net fluxes of (G) glucose, (H) lactate, (I) FFA, and (J) TAG across forearm muscle are shown. A positive flux indicates net uptake across the forearm muscle; a negative flux indicates net release. Values are given as mean ± SEM (n = 37).