Short-chain fatty acid biosynthesis (SCFA biosynthesis)

Short-chain fatty acid (SCFA) biosynthesis is a complex metabolic pathway primarily executed by the anaerobic gut microbiota through the fermentation of non-digestible dietary fibers (Morrison & Preston, 2016, Gut Microbes). The major end-products of this process are acetate, propionate, and butyrate, which play critical roles in maintaining intestinal health and systemic metabolic homeostasis (Koh et al., 2016, Cell). These SCFAs serve as the primary energy source for colonic epithelial cells and act as signaling molecules by binding to G protein-coupled receptors, specifically FFAR2 (GPR43) and FFAR3 (GPR41) (Tan et al., 2014, Adv Immunol). Additionally, SCFAs like butyrate function as potent inhibitors of histone deacetylases (HDACs), thereby regulating gene expression related to inflammation and cell proliferation (Roediger, 1980, Lancet). Dysregulation or diminished SCFA biosynthesis is strongly associated with the pathogenesis of inflammatory bowel disease, colorectal cancer, and metabolic disorders such as obesity and type 2 diabetes. Therapeutic strategies targeting this pathway include the administration of prebiotics, probiotics, or postbiotics to enhance SCFA production and restore gut barrier integrity. Because it represents a collective microbial process rather than a single human protein, it is categorized as a metabolic pathway rather than a discrete molecular drug target.

Other names

Short-chain fatty acid productionMicrobial fermentation of dietary fiberGut microbiota SCFA synthesisColonic fermentation

Modulation of the gut microbiome to increase the production of acetate, propionate, and butyrate, which subsequently activate host G protein-coupled receptors (FFAR2, FFAR3) and inhibit histone deacetylases (HDACs) to regulate inflammation and metabolism (Koh et al., 2016, Cell; Tan et al., 2014, Adv Immunol).