Intestinal flora regulating the occurrence and development of metabolic diseases

Abstract

The human gastrointestinal (GI) tract is a huge and complex micro-ecosystem, hosting trillions of microorganisms including but not limited to bacteria, fungi and viruses. The interactions and homeostasis among gut microorganisms, nutrient metabolism and epithelium of the GI tract are critical to host health. Disrupting the composition of GI microbiota may result in the development and progression of diseases. Gut bacteria, accounting for more than 90% of GI microorganisms, have shown diverse functions, such as affecting nutrient biosynthesis and bio-degradation, regulating drug metabolism and therapeutic efficacy, as well as maintaining intestinal mucosa structure and function. Numerous studies have demonstrated that the dysbiosis of gut bacteria may interrupt the intestinal and systemic immune homeostasis, leading to the development of various kinds of diseases. Furthermore, pathogenic metabolites released from gut bacteria may also interact with the host. Most metabolic diseases are closely associated with the alteration of gut bacterial structure and function. In recent years, researchers have established the link between metabolic diseases and dysbiosis of gut bacteria, such as type 2 diabetes and obesity. By performing the fecal microbiota transplantation, the obese feature could be reversed in mice, pigs and humans. The above discoveries suggested that fecal microbiota transplantation from healthy individuals could be a potential therapeutic strategy for several metabolic diseases. Diet intervention and exercise are still two important alternative and auxiliary therapeutic approaches for metabolic diseases together with other gut microbiota-related therapy. As food-derived nutrients could directly interact with gut microbiota and alter the composition, diversity and function of gut bacteria, we have found that both the level of dietary iron and host iron storage are closely associated with the composition of gut microbiota. Other than fecal transplantation-mediated therapy, probiotics have attracted attention as a supplement to improve the gut microenvironment for health-relevant applications, e.g., metabolic disease prevention and auxiliary therapy. Plenty of clinical investigations worldwide have provided first-hand data to support the therapeutic value of probiotics as a potential supplement for metabolic diseases. However, the therapeutic effect varies, which may due to the inconsistent probiotic strains and various dietary habits. In contrast to probiotics, probiotic fermentation metabolites (also named postbiotics) have shown its superior and beneficial effects beyond probiotics. Postbiotics generated by probiotics fermentation could be directly absorbed by the host and improve host systemic metabolic homeostasis. Our unpublished data suggest that postbiotics are able to effectively alleviate HFD-induced body weight gain, improve insulin sensitivity, decrease systemic inflammation and induce white adipocyte beigeing. In in vitro adipocyte culture system, purified postbiotics could suppress adipogenesis, and decrease lipid droplet formation. Overall, in this review, we summarized recent findings of the role of gut microbiota, especially the probiotics, in the development and progression of metabolic diseases such as obesity and type 2 diabetes.