Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

Abstract

ObjectiveThe gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans.MethodsMeal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition.ResultsAcute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release.ConclusionAs evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males.Trial Registrationclinicaltrials.gov NCT01633762

Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites

“…Similarly, bacterially produced short-chain fatty acids such as acetate, butyrate, and propionate not only serve as important energy sources for the intestinal epithelium and the liver but can also can modify insulin secretion, immune system function, appetite, and adipose function (Bouter et al, 2017; Canfora et al, 2015; Holmes et al, 2012; Perry et al, 2016). It is not surprising, therefore, that changes in the communities of organisms in the intestine can contribute to the pathogenesis of metabolic diseases, including obesity, type 2 diabetes, and the metabolic syndrome (Mikkelsen et al, 2015; Schroeder and Bäckhed, 2016). …”

Gut-Brain Cross-Talk in Metabolic Control

“…Finally, insights into a gut-brain circuitry involving microbiota and bile acid signaling suggest potential opportunities for innovative therapeutic intervention points (Degirolamo et al, 2014; Sayin et al, 2013). However, most reports find metabolic changes to be either rather modest in size, linked merely by association, or still awaiting replication, and massive alterations of gut microbiota in clinical studies have recently been documented not to impact energy homeostasis or systemic metabolism in humans (Mikkelsen et al, 2015; Reijnders et al, 2016). …”

Roles of the Gut in Glucose Homeostasis

“…The results suggest that the gut microbiota play a direct role in the reduction of adiposity observed after bariatric surgery (81) and that the changes were mainly due to weight loss. On the other hand, elimination of colonic microbiota has little or no effect on glucose metabolism in humans (82,83).…”