Microbiota-host short-chain fatty acid signaling axis (SCFA signaling axis)

The Microbiota-host short-chain fatty acid (SCFA) signaling axis is a complex biochemical pathway that mediates communication between the gut microbiome and the host's physiological systems [1, 3]. This axis is primarily driven by the microbial fermentation of dietary fibers into SCFAs, such as acetate, propionate, and butyrate, which serve as both energy sources and signaling molecules [4, 14]. These metabolites exert their effects by activating specific G protein-coupled receptors, including GPR41 (FFAR3), GPR43 (FFAR2), and GPR109A (HCAR2), and by acting as inhibitors of histone deacetylases (HDACs) to regulate gene expression [1, 5, 9]. The axis is fundamental to maintaining intestinal homeostasis, regulating immune cell function (particularly the induction of regulatory T cells), and modulating systemic processes like glucose metabolism and neuroinflammation [1, 4, 11]. Dysregulation of SCFA signaling is implicated in a wide range of pathologies, including inflammatory bowel disease, metabolic syndrome, cardiovascular disorders, and neurobehavioral conditions [1, 7, 10, 15]. Therapeutic interventions targeting this axis include prebiotics, probiotics, and small-molecule modulators of SCFA receptors, aiming to restore microbial balance and host-metabolic health [3, 16].

Other names

Gut microbiota-SCFA-host axisMicrobiota-SCFA-immune axisGut-SCFA-brain axisSCFA-GPCR signaling axis

Agonism of GPR41 (FFAR3), GPR43 (FFAR2), and GPR109A (HCAR2) receptors; inhibition of histone deacetylases (HDACs); modulation of gut hormone secretion (GLP-1, PYY); and regulation of immune cell differentiation (e.g., Treg induction).