Gut microbiota-short-chain fatty acid axis (Gut microbiota-SCFA axis)

The gut microbiota-short-chain fatty acid (SCFA) axis is a critical bidirectional communication system between the intestinal microbiome and the host, mediated primarily by the fermentation of dietary fibers into SCFAs like acetate, propionate, and butyrate [1, 6]. These metabolites serve as essential energy sources for colonocytes and act as potent signaling molecules by binding to specific G protein-coupled receptors, such as FFAR2 (GPR43) and FFAR3 (GPR41), and by inhibiting histone deacetylases (HDACs) [3, 4, 12]. This axis plays a fundamental role in maintaining gut barrier integrity, regulating systemic glucose and lipid metabolism, and modulating immune responses through the induction of regulatory T cells and anti-inflammatory cytokines [1, 15, 16]. Dysregulation of the gut microbiota-SCFA axis is implicated in a wide range of pathologies, including metabolic syndrome, inflammatory bowel disease, and neurodegenerative disorders [2, 6, 14]. Therapeutic strategies targeting this axis include the use of prebiotics, probiotics, and small-molecule agonists of SCFA receptors to restore metabolic and immune homeostasis [10, 12, 19]. Small-molecule modulators of SCFA receptors and prodrugs of butyrate are currently under investigation for their potential to treat chronic inflammatory and metabolic conditions [12, 19].

Other names

Microbiota-SCFA-host axisGut-microbiome-SCFA axisGut-SCFA-metabolic axisGut-SCFA-brain axisGut-SCFA-immune axis

Activation of G protein-coupled receptors (FFAR2, FFAR3, HCAR2), inhibition of histone deacetylases (HDACs), and activation of PPARγ.