Short-chain fatty acids (SCFAs)

Short-chain fatty acids — principally acetate, propionate and butyrate — are produced when anaerobic gut bacteria ferment dietary fibre and resistant starch that reaches the colon undigested. Butyrate is the preferred energy substrate for colonocytes, strengthens tight junctions and maintains mucosal barrier integrity, inhibits histone deacetylases (acting as an HDAC inhibitor) and signals via free fatty acid receptors GPR41, GPR43 and GPR109A to modulate immunity, appetite hormones and insulin secretion. Propionate travels primarily to the liver where it participates in gluconeogenesis and lipid regulation, while acetate enters systemic circulation. Reduced SCFA production — from low dietary fibre intake or loss of key producers such as Faecalibacterium prausnitzii and Roseburia intestinalis — is consistently associated with inflammatory bowel conditions, obesity and impaired glycaemic control, though translating this association into effective dietary or therapeutic interventions remains an active area of research.