The gut microbiome: a core regulator of metabolism

Abstract

The human body is inhabited by numerous bacteria, fungi, and viruses, and each part has a unique microbial community structure. The gastrointestinal tract harbors approximately 100 trillion strains comprising more than 1000 bacterial species that maintain symbiotic relationships with the host. The gut microbiota consists mainly of the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Of these, Firmicutes and Bacteroidetes constitute 70-90% of the total abundance. Gut microbiota utilize nutrients ingested by the host, interact with other bacterial species, and help maintain healthy homeostasis in the host. In recent years, it has become increasingly clear that a breakdown of the microbial structure and its functions, known as dysbiosis, is associated with the development of allergies, autoimmune diseases, cancers, and arteriosclerosis, among others. Metabolic diseases, such as obesity and diabetes, also have a causal relationship with dysbiosis. The present review provides a brief overview of the general roles of the gut microbiota and their relationship with metabolic disorders.

Keywords: diabetes; metabolism; obesity.

Figure 1

Short-chain fatty acid (SCFA) biosynthesis pathways.

Figure 2

Bile acid metabolism. The microbiota dehydroxylate primary bile acids, such as cholic acid and chenodeoxycholic acid, to secondary bile acids with 7a-dehydroxylase. Activation of the bile acid receptor FXR suppresses the expression of CYP7A1, a bile acid rate-limiting enzyme, via the induction of small heterodimer partner (SHP) expression in the liver to control bile acid synthesis. In addition, FXR activation in the intestine suppresses CYP7A1 and CYP8B1 expression via the induction of FGF15/19 expression.

Figure 3

Mechanisms of dysbiosis-induced impaired glucose metabolism. There are two major mechanisms of impaired glucose metabolism mediated by dysbiosis. One is the disruption of the intestinal barrier function, which causes LPS to enter circulation, inducing chronic inflammation and exacerbating insulin resistance, and the other is the effect of microbial metabolites. Increased branched-chain amino acids (BCAAs), imidazole propionate, and decreased short-chain fatty acids, such as butyrate, can affect insulin resistance in various organs, insulin secretion, and energy expenditure.