Short-chain fatty acid-producing pathways in gut microbiota (SCFA-producing pathways)

Short-chain fatty acid (SCFA)-producing pathways in the gut microbiota represent a critical metabolic interface between the host and its symbiotic bacterial community (Koh et al., 2016, Cell). These pathways involve the anaerobic fermentation of non-digestible dietary fibers and resistant starches into primary SCFAs, namely acetate, propionate, and butyrate (Louis & Flint, 2017, Environ Microbiol). These metabolites serve as essential energy sources for colonocytes and act as signaling molecules by binding to G protein-coupled receptors, such as GPR41 and GPR43, or by inhibiting histone deacetylases (HDACs) (Rios-Covian et al., 2016, Front Microbiol). Dysregulation of these pathways is linked to various conditions, including inflammatory bowel disease, metabolic syndrome, and colorectal cancer (Parada Venegas et al., 2019, Front Immunol). Therapeutic strategies targeting these pathways include the use of prebiotics, probiotics, and fecal microbiota transplantation to restore SCFA production and improve host health (Blaak et al., 2020, Nutrients). By modulating the gut environment, these interventions aim to enhance the production of beneficial metabolites that support immune homeostasis and metabolic regulation.

Other names

Microbial SCFA synthesisGut fermentation pathwaysAcetate, propionate, and butyrate production pathwaysMicrobiome-derived SCFA pathways

The primary mechanism involves the microbial conversion of complex carbohydrates into SCFAs, which then act as ligands for host G protein-coupled receptors (FFAR2 and FFAR3) to modulate immune and metabolic signaling, or enter host cells to inhibit histone deacetylases (HDACs), thereby regulating gene expression and maintaining intestinal barrier integrity (Koh et al., 2016, Cell; Parada Venegas et al., 2019, Front Immunol).