Gut microbiota found to determine exercise efficacy in diabetes prevention

A collaborative team of researchers led by those from the University of Hong Kong (HKU) recently identified the gut microbiota and its metabolites as key factors in determining exercise efficacy for diabetes prevention.

In the study, the gut microbiota of participants in the intervention group were significantly altered after exercise, with increased relative abundance seen in Firmicutes and other species. [Cell Metab 2019; pii:S1550-4131(19)30608-4] Decreased abundance of butyrate-producing genera Firmicutes was previously reported to be associated with obesity and type 2 diabetes mellitus (T2DM). [Nature 2015;528:262-266]

Likewise, there was a 3.5-fold increase of Lanchospiraceae bacterium (a butyrate producer) and a 43 percent decrease of Alistipes shahii after exercise. Increased Alistipes shahii is known to be associated with inflammation and enriched in obese patients. [J Clin Biochem Nutr 2016;59: 65-70]

The alteration in gut microbiota was significantly associated with percentage reduction of homeostatic model assessment for insulin resistance (HOMA-IR) (p<0.01, Adnois test), in which 19 species were significantly associated with improvements in glucose homeostasis and insulin sensitivity.

Apart from inducing alternations at a compositional level, exercise training also led to significant alterations in methane metabolism and carbon metabolism functional pathways. There was an increased transformation of arginine into ϒ-aminobutyric acid, suggestive of favourable utilization of amino acids. Exercise intervention also resulted in differential changes in saccharolytic fermentation, with significant increases in genes involved in propionate biosynthesis from glycolytic products. In contrast, there was a high abundance of genes encoding enzymes responsible for degradation of amino acids that maintain insulin sensitivity in nonresponders to exercise.  

Significant reductions in branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), which hamper insulin sensitivity, were detected in faecal samples in responders to exercise training. Consistent with the changes in faecal metabolites, there were decreases in circulating levels of BCAAs and AAAs in responders after exercise intervention.

In this study, 39 medication-naïve men with prediabetes were randomized to either a sedentary control group or an intervention group. Individuals in the intervention group received 12 weeks of supervised exercise training, and were further evaluated for exercise responsiveness. A model was established based on the microbiome signatures before exercise to predict exercise outcomes in terms of glycaemic control and insulin sensitivity. The study was done in collaboration with the Guangdong Pharmaceutical University.

Dysbiosis of gut microbiota is known to have an important role in the pathogenesis of insulin resistance and T2DM, with compositional and functional changes of gut microbiota found in individuals with T2DM or prediabetes. Exercise is a cost-effective intervention for diabetes and prediabetes, with recent studies showing a modulatory effect on gut microbiota in both humans and animals. Nevertheless, the efficacy of exercise can be hindered by the phenomenon of exercise resistance. [Gastroenterology 2017;152:1671-1678; Diabetologia 2018;61:810-820; Nature 2012;490:55-60]

“Our study uncovered gut microbiota and its metabolism as key molecular transducers to the heterogenous adaption to exercise intervention on glucose metabolism and insulin sensitivity,” concluded researchers. “This finding, together with the model of the predictive value of baseline microbial signatures for individualized responsiveness to exercise, may facilitate clinical implementation of personalized lifestyle intervention for diabetes management.”