Dataset Information

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.

SUBMITTER: Reijnders D

PROVIDER: S-EPMC6189533 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Reijnders Dorien D Goossens Gijs H GH Hermes Gerben D A GDA Smidt Hauke H Zoetendal Erwin G EG Blaak Ellen E EE

Obesity facts 20180809 4

<h4>Objective</h4>To investigate the impact of gut microbiota manipulation on fasting and postprandial skeletal muscle metabolism in humans.<h4>Methods</h4>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.<h4>R ...[more]

PMID: 30089301

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Project description:BackgroundMacrolides are commonly prescribed for respiratory infections and asthma-like episodes in children. While their clinical benefits have been proved, concerns regarding the side-effects of their therapeutic use have been raised. Here we assess the short- and long-term impacts of azithromycin on the gut microbiota of young children.MethodsWe performed a randomized, double-blind, placebo-controlled trial in a group of children aged 12-36 months, diagnosed with recurrent asthma-like symptoms from the COPSAC2010 cohort. Each acute asthma-like episode was randomized to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo. Azithromycin reduced episode duration by half, which was the primary end-point and reported previously. The assessment of gut microbiota after treatment was the secondary end-point and reported in this study. Fecal samples were collected 14 days after randomization (N = 59, short-term) and again at age 4 years (N = 49, long-term, of whom N = 18 were placebo treated) and investigated by 16S rRNA gene amplicon sequencing.FindingsShort-term, azithromycin caused a 23% reduction in observed richness and 13% reduction in Shannon diversity. Microbiota composition was shifted primarily in the Actinobacteria phylum, especially a reduction of abundance in the genus Bifidobacterium. Long-term (13-39 months after treatment), we did not observe any differences between the azithromycin and placebo recipients in their gut microbiota composition.InterpretationAzithromycin treatment induced a perturbation in the gut microbiota 14 days after randomization but did not have long-lasting effects on the gut microbiota composition. However, it should be noted that our analyses included a limited number of fecal samples for the placebo treated group at age 4 years. FUND: Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation, China Scholarship Council.

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Dataset Information

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

Publications

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

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