Microbial fatty acids (SCFA)

Microbial fatty acids, primarily short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate, are metabolic products generated by the gut microbiota through the fermentation of non-digestible carbohydrates (Koh et al., 2016). These molecules function as critical signaling mediators between the microbiome and the host, influencing systemic physiology by acting as ligands for specific G protein-coupled receptors, including Free fatty acid receptor 2 (FFAR2) and Free fatty acid receptor 3 (FFAR3) (Bolognini et al., 2016). Beyond receptor activation, SCFAs like butyrate serve as potent inhibitors of histone deacetylases (HDACs), thereby regulating gene expression related to inflammation and cell proliferation (Davie, 2003). In clinical contexts, microbial fatty acids are associated with the maintenance of intestinal barrier integrity and the modulation of immune responses, with deficiencies linked to inflammatory bowel disease, metabolic disorders, and colorectal cancer (Tan et al., 2014). Therapeutic approaches targeting this axis include the use of prebiotics, probiotics, and postbiotic SCFA mimetics to restore metabolic and immunological homeostasis (Rooks & Garrett, 2016).

Other names

Short-chain fatty acidsSCFAsVolatile fatty acidsBacterial fatty acidsGut-derived fatty acids

Microbial fatty acids act as endogenous ligands for G protein-coupled receptors, specifically Free fatty acid receptor 2 (FFAR2) and Free fatty acid receptor 3 (FFAR3), which modulate immune cell chemotaxis and metabolic hormone release (Brown et al., 2003). Additionally, they function as epigenetic modulators by inhibiting histone deacetylases (HDACs), particularly HDAC1 and HDAC3, leading to increased histone acetylation and altered transcription of anti-inflammatory genes (Davie, 2003). In the gut, butyrate also serves as the primary oxidative fuel for colonic epithelial cells, supporting mucosal barrier function (Koh et al., 2016).