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

• Published in: Obesity facts Vol. 11; no. 4; pp. 318 - 326
• Main Authors: Reijnders, Dorien, Goossens, Gijs H., Hermes, Gerben D.A., Smidt, Hauke, Zoetendal, Erwin G., Blaak, Ellen E.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-01-2018; S. Karger GmbH; Karger Publishers
• Subjects: Amoxicillin - pharmacology; Anti-Bacterial Agents - pharmacology; Antibiotics; Body fat; Catheters; Clinical trials; Double-Blind Method; Double-blind studies; Fasting; Fatty acids; Fatty Acids, Nonesterified - metabolism; Forearm; Gastrointestinal Microbiome - drug effects; Glucose; Glucose Intolerance - complications; Glucose Intolerance - metabolism; Glucose Intolerance - microbiology; Glycerol; Humans; Insulin Resistance; Kinases; Laboratorium voor Microbiologie; Lipids; Male; Metabolism; Metabolites; Microbiological Laboratory; Microbiologie; Microbiology; Microbiota; Middle Aged; Muscle, Skeletal - chemistry; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Musculoskeletal system; Obesity; Obesity - complications; Obesity - metabolism; Obesity - microbiology; Oxidation; Phylogenetics; Placebos; Plasma; Postprandial Period; Research Article; Skeletal muscle; Vancomycin - pharmacology; VLAG; WIMEK; United States > US; Obesity; Insulin resistance; Microbiota; Antibiotics; Skeletal muscle
• ISSN: 1662-4025; 1662-4033
• DOI: 10.1159/000492114

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.