Short-Chain Fatty Acid Receptor and Its Contribution to Glucagon-Like Peptide-1 Release

Abstract

Background: Gut microbiota affects host homeostasis and dysbiosis causes host diseases. Therefore, uncovering the sensing mechanism of bacterial metabolites such as short-chain fatty acid (SCFA) may help us to understand the host-microbiota interaction both in physiological and nonphysiological conditions. Summary: The colonic lumen is continually exposed to many kinds of chemicals, including beneficial and harmful compounds that are produced by gut microbiota in addition to ingested nutrients. In the mammalian colon SCFAs such as acetate, propionate and butyrate are produced by bacterial fermentation and reach about 100 m<smlcap>M</smlcap> under physiological conditions. In this decade, SCFA receptor genes and their expression in the intestine have been identified as free fatty acid receptor (FFA)2 and FFA3. The FFAs are located in colonic enteroendocrine L cells producing and releasing an insulinotropic hormone, glucagon-like peptide-1 (GLP-1), and an anorectic hormone, peptide YY. Recent in vivo and in vitro studies suggest that SCFAs stimulate gut hormone secretion. Therefore, the SCFA-FFA signal is likely to be important for gut physiological functions. Key Message: Colonic epithelial cells express chemical receptors that detect the luminal contents, particularly bacterial metabolites, and may be involved in the host's energy metabolism via GLP-1 release, as well as the mucosal defense system.

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

“…SCFAs stimulate the secretion of glucagon-like peptides 1 and 2 via ligation of glucagon-like peptide-43 [137][138][139] leading to decreased epithelial permeability and increased mucosal antibacterial defenses [140]. Glucagon-like peptides 1 and 2 improve barrier function via a number of different mechanisms, including via the stimulation of L class enteroendocrine cells and the inhibition of apoptosis of intestinal epithelial cells [141].…”

An Enteral Formula Containing Fermented Milk Products and Prebiotics Promotes Glucagon-Like Peptide-1 Secretion via Short Chain Fatty Acid Signaling

“…PF contains indigestible oligosaccharides and more water-soluble dietary fiber than SF, and the increase in cecal undigested fermentation substrates may promote the production of SCFAs such as acetic acid, propionic acid, and butyric acid (Table 2). In addition, some researchers have reported the increase in the number of small intestine L cells that express SCFA receptors and in secreted GLP-1 because of the long-term ingestion of fructo-oligosaccharides, a type of indigestible oligosaccharide that produces SCFAs upon intestinal fermentation [21]. A similar change occurs because of the ingestion of PF containing GOS, another type of indigestible oligosaccharide (unpublished data).…”

The Local Defender and Functional Mediator: Gut Microbiome

“…Some research have indicated that SCFAs especially butyrate as the preferred substrate for the epithelial cells, play a part in the integrity of the mucosal and epithelial layers and gut barrier, which are associated with the proliferation, differentiation, and apoptosis of cell, increased MUC2 gene expression, and antioxidant activity [91]. Apart from the stimulation of motility demonstrated could be through the release of 5-hydroxytryptamine (5-HT) through stimulating 5-HT3 receptors located on the vagal sensory fibers in rats, and secretory activity via the enteric nervous system, SCFAs can curb appetite and sensitize insulin by promoting the production of satietyinducing hormones, including peptide YY and glucagon-like peptide 1 through activating G-protein coupled receptor41 and 43 (GPR41 and GPR43) and leptin secreted from adipocyte, as well as the appetite inhibition of acetate across BBB on hypothalamus and gluconeogenesis facilitation of butyrate [92][93][94][95]. The effects of acetate, propionate and butyrate on host physiology are distinct and often vary.…”