Volatile (Short-Chain) Fatty Acids in Gut Physiology: Literature Review

Open access*Corresponding author Hanaa H El-Sayed: 01008825869Email: [email protected]: 15 November 2025Accepted: 22 November 2025Published: 2 December 2025Citation: El-Sayed HH (2025): Volatile (Short-Chain) Fatty Acids in Gut Physiology: Literature ReviewBNNI, (2) 23-39 doi:10.21608/bnni.2025.468385Short-chain fatty acids (SCFAs), often called volatile fatty acids (VFAs) in older studies, are low-molecular-weight carboxylic acids, mainly acetate, propionate, and butyrate, produced by microbial fermentation of dietary fiber and other nondigestible substrates in the gastrointestinal tract. SCFAs play a central role in connecting diet, microbiota composition, and host physiology: locally, they fuel colonocytes, maintain barrier integrity, regulate fluid and electrolyte transport, and influence gut motility and mucosal and systemic immune responses; systemically, they affect hepatic gluconeogenesis, lipogenesis, and endocrine signaling through GPCRs and epigenetic mechanisms (such as histone deacetylase inhibition). Changes in SCFA production, absorption, or signaling have been linked to metabolic disorders, inflammatory and autoimmune diseases, gastrointestinal pathology, and emerging effects outside the gut. This review compiles recent evidence on the definition and composition of SCFAs, microbial sources and production pathways, epithelial absorption and transporters, the metabolic fates of individual SCFAs, their physiological functions within the digestive system, and broader impacts on human health and disease. Key knowledge gaps and promising strategies for therapeutic manipulation of SCFA levels (including dietary fiber, prebiotics, probiotics, and targeted SCFA delivery) are discussed.