The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release

Abstract

The microbial community of the gut conveys significant benefits to host physiology. A clear relationship has now been established between gut bacteria and host metabolism in which microbial-mediated gut hormone release plays an important role. Within the gut lumen, bacteria produce a number of metabolites and contain structural components that act as signaling molecules to a number of cell types within the mucosa. Enteroendocrine cells within the mucosal lining of the gut synthesize and secrete a number of hormones including CCK, PYY, GLP-1, GIP, and 5-HT, which have regulatory roles in key metabolic processes such as insulin sensitivity, glucose tolerance, fat storage, and appetite. Release of these hormones can be influenced by the presence of bacteria and their metabolites within the gut and as such, microbial-mediated gut hormone release is an important component of microbial regulation of host metabolism. Dietary or pharmacological interventions which alter the gut microbiome therefore pose as potential therapeutics for the treatment of human metabolic disorders. This review aims to describe the complex interaction between intestinal microbiota and their metabolites and gut enteroendocrine cells, and highlight how the gut microbiome can influence host metabolism through the regulation of gut hormone release.

Keywords: CCK; GIP; GLP-1; PYY; enteroendocrine cells; metabolism; microbiome; serotonin.

FIGURE 1

Microbial regulation of host metabolism via gut hormone release. Gut microbiota signal to nearby enteroendocrine (EE) cells via a range of microbial metabolites, including short chain fatty acids and secondary bile acids, and structural components. These EE cells release important metabolically active hormones, such as GLP-1, PYY, GIP, 5-HT, and CCK, which influence key metabolic processes including glucose metabolism, insulin sensitivity, adiposity, and feeding behavior. In turn, dietary components impact the composition of gut microbiota, which may have further downstream consequences on gut hormone secretion and host metabolism.

FIGURE 2

Microbial signaling to enteroendocrine cells. Resident microbiota within the intestinal lumen signal to enteroendocrine (EE) cells via multiple pathways. Firstly, microbiota convert indigestible carbohydrates to short chain fatty acids (SCFA), which in turn signal to EE cells via free fatty acid receptors 2 or 3 (FFAR2/3) or by activation of nuclear histone deacetylases (HDAC). Secondly, microbiota convert primary (1°) bile acids to secondary (2°) bile acids, such as deoxycholate, which then signal to EE cells via the membrane G protein-coupled bile acid receptor, TGR5, or nuclear FXR. Finally, structural components of microbiota, such as flagella, and the endotoxin lipopolysaccharide (LPS), signal to toll-like receptors (TLRs).