Short-Chain Fatty Acid Metabolism in Colorectal Health

Short-chain fatty acids (SCFAs) are key microbial metabolites generated in the colon through fermentation of indigestible carbohydrates. The principal SCFAs—acetate, propionate and butyrate—serve as energy substrates for colonocytes, strengthen epithelial barrier function, and modulate immune and inflammatory pathways. Uptake of SCFAs by epithelial cells occurs via monocarboxylate transporters and passive diffusion. Intracellularly, butyrate is oxidised to acetyl-CoA, fuelling mitochondrial respiration and sustaining mucosal integrity. Systemically, SCFAs engage G-protein-coupled receptors (notably GPR41 and GPR43) on immune and stromal cells, influencing cytokine release and cellular proliferation. Perturbations in SCFA production or host uptake are associated with dysbiosis, mucosal inflammation and increased colorectal cancer risk. A comprehensive understanding of the pathways governing SCFA synthesis, absorption and downstream signalling underpins preventive and therapeutic strategies for colorectal disorders.

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Short-Chain Fatty Acid Metabolism in Colorectal Health publication trend

The graph below shows the total number of articles in short-chain fatty acid metabolism in colorectal health across all publications each year (not limited to Nature Index journals).

Technical terms

Short-chain fatty acids (SCFAs): Microbial fermentation products of dietary fibres, primarily acetate, propionate and butyrate, that fuel colonocyte energy metabolism and signal via G-protein-coupled receptors.

Colonocyte: Epithelial cell lining the colon responsible for nutrient absorption, barrier formation and innate immune responses.

Gut microbiota: Community of bacteria, archaea and fungi resident in the gastrointestinal tract that drive fermentation of complex carbohydrates and influence host physiology.

Fermentation: Anaerobic microbial process converting non-digested substrates into SCFAs and gases within the large intestine.

Epithelial barrier integrity: The functional and structural state of the mucosal lining preventing translocation of luminal antigens and microbes into underlying tissues.

References

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2. Detection of changes in regional colonic fermentation in response to supplementing a low FODMAP diet with dietary fibres by hydrogen concentrations, but not by luminal pH. Alimentary Pharmacology & Therapeutics (2023).
3. A ação dos ácidos graxos de cadeia curta na cicatrização de anastomoses colônicas: estudo experimental em ratos. Acta Cirúrgica Brasileira (2000).