The role of the gut microbiome and its metabolites in metabolic diseases

Abstract

It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases, while in recent years, accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases, including obesity, type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular disease and so on. Numerous microorganisms dwell in the gastrointestinal tract, which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances, thus acting as a link between the gut microbiome and its host. The gut microbiome is shaped by host genetics, immune responses and dietary factors. The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases. Therefore, targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future. This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases. Furthermore, recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.

Keywords: gut microbiome; immune regulation; metabolic diseases; metabolism; metabolite.

Figure 1

The modulation of the gut microbiome-bile acid-FXR axis. Treatment with metformin decreased the abundance of Bacteroides fragilis and increased the level of GUDCA, thereby suppressing intestinal FXR signaling. Gly-MCA inhibited intestinal FXR signaling and altered host liver lipid metabolism. CAPE supplementation inhibited bacterial BSH to increase the levels of intestinal TβMCA, which selectively suppressed intestinal FXR signaling and reduced the level of ceramide, thereby reducing hepatic gluconeogenesis in mice. Bacteroides vulgatus can deconjugate GDCA and TUDCA synthesized in individuals with PCOS. GDCA can induce ILC3 secretion of IL-22 through TGR5, GATA binding protein 3, and IL-22, in turn improving the PCOS phenotype. CAPE, caffeic acid phenethyl ester; GUDCA, glycoursodeoxycholic acid; Gly-MCA, glycine-β-muricholic acid; TβMCA, tauro-β-muricholic acid; TUDCA, tauroursodeoxycholic acid; GDCA, glycodeoxycholic acid; ILC3, intestinal group 3 innate lymphoid cell; PCOS, polycystic ovary syndrome