Prokopis Konstanti is a PhD candidate focusing on the molecular analysis of microbial communities, the role of microbes in human physiology and the gut-brain axis in the group of Molecular Ecology at the Laboratory of Microbiology at the Wageningen University (the Netherlands).
Developing type 2 diabetes is for a large part influenced by your diet but also genes. However, a recent study has now shown that your gut microorganisms might also play an important role in the risk of developing type 2 diabetes (T2D). The article published in Nature Genetics entitled “Causal relationships among the gut microbiome, short-chain fatty acids (SCFA’s) and metabolic diseases”, claims evidence that bacterial metabolites such as SCFA’s are able to influence insulin levels and increase the risk of getting T2D.
Various studies have suggested that increased SCFA production benefits the host by exerting anti-obesity and antidiabetic effects, however, results of different studies are not always in agreement. Moreover, there is also evidence that increased production of SCFAs in the gut might be related with obesity, due to energy accumulation. Resolving these conflicting findings requires a detailed understanding of the causal relationships between the gut-microbiome and host energy metabolism, and the present study contributes to this.
The authors analysed data from a large population study based in Groningen (The Netherlands), comprising 952 individuals with known genetic data, as well as information on parameters associated with metabolic traits such as BMI and insulin sensitivity. In addition, data was acquired for the type and the function of the bacteria which were present in the gut of the study participants. Combining this data, the authors tried to answer the question whether changes in microbiome features causally affect metabolic traits or vice versa?
A technique called Mendelian randomization (MR) which is increasingly accepted to establish cause-effect relationships in the onset of diseases, was applied. The primary outcome of the analysis was that host genes influence the production of the SCFA butyrate in the gut, which is associated with improved insulin response in the blood after an oral glucose tolerance test. In addition, abnormalities in the production or absorption of propionate, another SCFA, were causally related to an increased risk of T2D.
So far available data suggest that overweight humans or those with type 2 diabetes may have different microorganisms in their gut compared to healthy people. These microorganisms which are commonly found in healthy people are absent from the T2D patients. Whether the differences in the microbiota between healthy and T2D patients are an effect of the disease development or account for causality is challenging to be answered. With the data from the present study, authors are able to go one step further and demonstrate potential routes by which microorganisms are able to regulate our metabolic status underlying their importance for our wellbeing.
Collectively the present article suggests that production of bacterial SCFA’s play a pivotal role in the regulation of metabolic traits such as blood insulin levels and are associated with the onset of T2D. Since the study was observational and did not include any T2D patients, confirmation of the results is essential. Follow up studies including T2D patients would be highly informative. With the rising prevalence of obesity in adults, which is reaching epidemic levels, the prevalence of T2D will also continue to rise. In the past years, scientists have mainly focused on the role of human gene data, but this has not lead to major breakthroughs. Maybe knowledge on the microbiome will elucidate molecular mechanisms which can be translated to novel effective treatments for metabolic disorders such as T2D.
References
1.) Sanna, S., van Zuydam, N. R., Mahajan, A., Kurilshikov, A., Vila, A. V., Võsa, U., . . . Oosting, M. (2019). Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases Nature genetics, 1.