Gut microbiota provide key to exercise efficacy to treat diabetes

24 December 2019

It has long been known that exercise is the most cost-effective way to prevent and treat Type 2 diabetes, a leading cause of morbidity and mortality worldwide. However, exercise does not work for everyone.

A collaborative team of scientists from Hong Kong, Germany, and mainland China, led by Professor Xu Aimin (Croucher Senior Research Fellowship 2016), has discovered a reason why: the effectiveness of exercise is related to the composition of microbiota in the gut.

A total of 39 Chinese men with impaired glucose metabolism (pre-diabetes), who did not take any medication, participated in a 12-week individualised but similar exercise programme. By the end of the programme, all participants exhibited a similar degree of body weight and fat mass reduction. However, only 70 per cent demonstrated significant improvements in glucose metabolism and insulin sensitivity.

The team, led by Xu, Chair Professor in the Li Ka Shing Faculty of Medicine, University of Hong (HKU) and Director of the State Key Laboratory of Pharmaceutical Biotechnology, HKU, used advanced integrative analysis and discovered obvious differences in exercise-induced alterations in gut microbiota and its metabolites at both the compositional and functional levels between responders and non-responders.

The findings, published in Cell Metabolism, suggest that the right mix and diversity of gut microbiota can have an influential effect on individuals’ metabolic health and the degree to which they respond to the low-cost intervention of exercise.

The team found that the post-exercise microbiome of responders was active in breaking down amino acids that promote insulin resistance, which is beneficial to individuals looking to improve or optimise their blood glucose profile.

Conversely, a different set of microbiome was found in post-exercise non-responders. Their microbiome resulted in the breaking down of substances that promote insulin sensitivity, working counter to the intended exercise objective.

When transplanting the participants’ gut microbes into obese mice, blood-sugar levels dropped in the mice that received post-exercise microbiomes from responders, whereas animals receiving bacteria from non-responders showed no such improvement.

Interestingly, it was found that oral supplementation with short-chain fatty acids can restore the ability of gut microbiota from non-responders to improve glucose metabolism and insulin sensitivity. Furthermore, a prediction model based on microbiota and its metabolites before exercise accurately predicted personalised glycaemic responses to exercise in another 30 subjects with pre-diabetes.

This study suggested that microbiota and its metabolites serve as important contributors to the metabolic benefits of exercise intervention, and identified maladaptation of gut microbiota as a “culprit” for those individuals who do not respond to exercise. They can also indicate whether an individual could benefit from exercise or whether additional modulations targeting gut microbiota are needed to boost health and assist responsiveness to exercise.

This was one of the first interventional randomised controlled trial studies providing clear evidence of the role of gut microbiota on metabolic health. The findings also offer new insight for clinicians and exercise specialists on targeting the microbiota of exercise non-responders as another means of enhancing therapeutic interventions.

Professor Aimin Xu holds joint appointments in the Department of Medicine and Department of Pharmacology & Pharmacy, and directs the State Key Laboratory of Pharmaceutical Biotechnology at the University of Hong Kong. He received his BS (Hons) in Medicine at Anhui Medical University in mainland China in 1989 and earned his PhD in Biochemistry and Molecular Biology at the University of Auckland in New Zealand in 1999. He received postdoctoral training at the School of Biological Sciences, University of Auckland, working on proteomic identification of novel adipocyte-derived factors involved in obesity and insulin resistance. Professor Xu Aimin received his Croucher Senior Research Fellowship in 2016.

To view Professor Xu’s Croucher profile, please click here.