Gut microbiota metabolite regulation of host defenses at mucosal surfaces: implication in precision medicine

Abstract

Abstract The gut microbiota has a well-established role in the regulation of host homeostasis. Multiple factors control the composition and function of the microbiota. The westernization of diet, a shift away from nutrient-dense foods toward diets high in saturated fats, has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease (IBD). Diet is critical in the development and maintenance of a healthy microbiome, where dietary fiber (found in the highest amounts in fruits, vegetables, and legumes) is metabolized by the microbiome. In turn, the bacterial metabolites of dietary fiber, short chain fatty acids (SCFAs), regulate gut homeostasis. SCFAs engage G-protein coupled receptors (GPRs) and act as histone deacetylase inhibitors (HDACi) to module epithelial and immune cell functions in the intestines, where they generally promote an anti-inflammatory state. This review highlights the functions of SCFAs and their roles in the pathogenesis of IBD to provide insights into their potential therapeutic application for the treatment of IBD for the purposes of precision medicine.