Mechanisms of Gastrointestinal Hormone Secretion Regulated by Gut Microbiota -Derived Metabolites

Abstract

Glucagon-like peptide‑1 (GLP‑1) is a gastrointestinal hormone secreted by enteroendocrine L cells. Nutrients in the intestinal lumen directly stimulate L cells to trigger GLP‑1 secretion, which plays a crucial role in blood glucose regulation and appetite suppression. Furthermore, the gut microbiota metabolizes ingested nutrients into a diverse array of metabolites within the lumen. These microbiota‑derived metabolites have also been shown to activate L cells and modulate GLP‑1 secretion.

This review focuses on specific gut microbiota-derived metabolites, including S‑equol (a product of soy isoflavone metabolism) and the secondary bile acid deoxycholic acid and taurine (released via bile acid deconjugation), to describe their effects on L-cell function and GLP‑1 secretion. These metabolites promote GLP-1 release by activating G protein–coupled receptors and transporters expressed on L cells. We also address short‑chain fatty acids (SCFAs), the most well-characterized microbiota-derived metabolites known to enhance GLP‑1 secretion. While SCFAs have been widely reported to activate G protein–coupled receptors on L cells and stimulate GLP‑1 secretion, we have demonstrated that SCFAs can conversely attenuate GLP‑1 secretion depending on the specific L-cell microenvironment.

These findings provide important insights into the complex interplay among dietary components, microbiota-derived metabolites, and L-cell-mediated endocrine responses, thereby deepening our understanding of how these factors collectively shape host metabolism.

graphical abstract