The Potential Role of Gut Microbiota in the Pathogenesis of Type 2 Diabetes Mellitus via Epigenetics and Inflammasome

Abstract

The gut microbiota that comprises over 100 trillion microorganisms with a weight of about 1-2 kg is regarded as one of the most crucial players in the regulation of the metabolic health of host organisms. In recent years, the incidence of type 2 diabetes mellitus (T2DM), characterized by high levels of sugar in the blood, has been exponentially increasing due to obesity and other lifestyle risk factors. It was shown that dysbiosis, change in the overall composition, and diversity of gut microflora can result in T2DM. Conversely, the microbial composition can also influence the epigenetics of the host organism (DNA methylation as well as histone modifications), which might have a potential effect on the metabolic health of the individual. Another mechanism of gut microbiota in the development of T2DM is through the involvement of nucleotide-binding oligomerization domain, Leucine-rich Repeat, and Pyrin domain containing 3 (NLRP3) inflammasome, a part of the innate immune system. NLRP3 inflammasome produces inflammatory cytokines, promoting the secretion of microbial antigens in the intestinal epithelium. Therefore, it is important to understand the possible connecting link between gut microbiota and T2DM that might help in the modulation of gut microflora to better understand the disease. In this review, the role of gut microbiota in the pathogenesis of T2DM will be discussed.

Keywords: Microbiota; diabetes mellitus; dysbiosis; epigenetics; gut; inflammasome.