Protective Effects of Short-Chain Fatty Acids on Gut Mucosa
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Background: Short-chain fatty acids (SCFAs) are key metabolites produced by microbial fibre fermentation and act as an epigenetic link between diet and gene expression. SCFA production is highly dependent on dietary fiber diversity to support a healthy microbial ecosystem. Through the gut-brain axis, SCFAs influence cognitive function by altering the brain's response to food signals and reducing systemic inflammation. Objective: This study aimed to determine the effects of short-chain fatty acids on the gastrointestinal mucosa and their relationships with diet, fibre, and the gut-brain axis. Methods: This study used a systematic review guided by PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The literature was searched across three databases: PubMed, EBSCO, and Scopus. The study selection process followed predetermined inclusion and exclusion criteria, and the results of included studies were systematically analyzed. Results: A total of 20 studies were analyzed. Most studies show that SCFAs can protect the gastrointestinal mucosa through a healthy microbiota balance and a proper diet, including a high-fiber diet. Conclusion: A high-fibre diet can produce SCFAs that regulate metabolic/inflammatory genes, improve intestinal mucosal function, enhance glucagon-like peptide-1 (GLP-1) secretion, improve glycemic/appetite control, and reduce the brain's response to high-calorie foods. It also lowers high-sensitivity C-reactive protein (high-sensitivity C-reactive protein (high-sensitivity C-reactive protein (high-sensitivity C-reactive protein (high-sensitivity C-reactive protein (hs-CRP))))), improving stress, anxiety, and mental health.
Contribution to Sustainable Development Goals (SDGs):
SDG 3- Good Health and Well-Being
SDG 4:- Quality Education
SDG 12 – Responsible Consumption and Production
[1] Nshanian M, Gruber JJ, Geller BS, Chleilat F, Lancaster SM, White SM, et al. Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression. Nat Metab. 2025;7(1):196–211.
[2] Liu P, Liu Z, Wang J, Wang J, Gao M, Zhang Y, et al. Immunoregulatory role of the gut microbiota in inflammatory depression. Nat Commun. 2024;15(1).
[3] Medawar E, Beyer F, Thieleking R, Haange SB, Rolle-Kampczyk U, Reinicke M, et al. Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial. Gut. 2023;73(2):298–310.
[4] Bailey MA, Thompson S V., Mysonhimer AR, Bennett JN, Vanhie JJ, De Lisio M, et al. Dietary fiber intake and fecal short-chain fatty acid concentrations are associated with lower plasma lipopolysaccharide-binding protein and inflammation. Am J Physiol - Gastrointest Liver Physiol. 2023;324(5):G369–77.
[5] van Kalkeren CAJ, van Deuren T, Coenjaerds MMJ, Galazzo G, Barnett DJM, Penders J, et al. Effects of a slowly fermentable fiber mixture against the background of a high-protein diet on insulin sensitivity and metabolic health in individuals with overweight: a randomized, placebo-controlled trial. Gut Microbes. 2026;18(1).
[6] Hall CV, Hepsomali P, Dalile B, Scapozza L, Gurry T. Effects of a diverse prebiotic fibre blend on inflammation, the gut microbiota and affective symptoms in metabolic syndrome: A pilot open-label randomised controlled trial. Br J Nutr. 2024;132(8):1002–13.
[7] Shaidullov IF, Sorokina DM, Sitdikov FG, Hermann A, Abdulkhakov SR, Sitdikova GF. Short chain fatty acids and colon motility in a mouse model of irritable bowel syndrome. BMC Gastroenterol [Internet]. 2021;21(1):1–12. Available from: https://doi.org/10.1186/s12876-021-01613-y
[8] Xie Z, He W, Gobbi A, Bertram HC, Nielsen DS. The effect of in vitro simulated colonic pH gradients on microbial activity and metabolite production using common prebiotics as substrates. BMC Microbiol. 2024;24(1):1–14.
[9] Peterson CT, Perez Santiago J, Iablokov SN, Chopra D, Rodionov DA, Peterson SN. Short-Chain Fatty Acids Modulate Healthy Gut Microbiota Composition and Functional Potential. Curr Microbiol [Internet]. 2022;79(5):1–13. Available from: https://doi.org/10.1007/s00284-022-02825-5
[10] Li S, Ma X, Mei H, Chang X, He P, Sun L, et al. Association between gut microbiota and short-chain fatty acids in children with obesity. Sci Rep. 2025;15(1):1–11.
[11] Chenghan M, Wanxin L, Bangcheng Z, Yao H, Qinxi L, Ting Z, et al. Short-chain fatty acids mediate gut microbiota–brain communication and protect the blood–brain barrier integrity. Ann N Y Acad Sci. 2025;1545(1):116–31.
[12] van de Wouw M, Boehme M, Lyte JM, Wiley N, Strain C, O’Sullivan O, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. J Physiol. 2018;596(20):4923–44.
[13] Bilotta AJ, Ma C, Yang W, Yu Y, Yu Y, Zhao X, et al. Propionate Enhances Cell Speed and Persistence to Promote Intestinal Epithelial Turnover and Repair. Cmgh. 2021;11(4):1023–44.
[14] Karl JP, Fagnant HS, Radcliffe PN, Wilson M, Karis AJ, Sayers B, et al. Gut microbiota-targeted dietary supplementation with fermentable fibers and polyphenols prevents hypobaric hypoxia-induced increases in intestinal permeability. Am J Physiol - Regul Integr Comp Physiol. 2025;329(3):R378–99.
[15] Gill PA, Muir JG, Gibson PR, Van Zelm MC. A randomized dietary intervention to increase colonic and peripheral blood SCFAs modulates the blood B- and T-cell compartments in healthy humans. Am J Clin Nutr. 2022;116(5):1354–67.
[16] Zhao H, Zhou Y, Xu J, Zhang Y, Wang H, Zhao C, et al. Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK / STAT3 / FOXO3 axis inactivation. 2024;1–17.
[17] Wang Y, Wymond B, Tandon H, Belobrajdic DP. Swapping White for High-Fibre Bread Increases Faecal Abundance of Short-Chain Fatty Acid-Producing Bacteria and Microbiome Diversity: A Randomized, Controlled, Decentralized Trial. Nutrients. 2024;16(7).
[18] Malcomson FC, Louca P, Nelson A, Willis ND, Mc Callum I, Xie L, et al. Effects of non-digestible carbohydrates on gut microbiota and microbial metabolites: a randomised, controlled dietary intervention in healthy individuals. Br J Nutr. 2024;132(11):1433–45.
[19] Szczuko M, Duliban G, Drozd A, Sochaczewska D, Pokorska-Niewiada K, Zi?tek M. The Association of Short-Chain Fatty Acids with the Occurrence of Gastrointestinal Symptoms in Infants. Int J Mol Sci. 2024;25(23):1–13.
[20] Seethaler B, Nguyen NK, Basrai M, Kiechle M, Walter J, Delzenne NM, et al. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am J Clin Nutr. 2022;116(4):928–42

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