El-Salhy M, Shin CM, Kim YS, Hatlebakk JG. World Journal of Translational Medicine. 2026;12(3):122740. DOI: 10.5528/wjtm.122740
Background & Rationale
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that reduces quality of life and carries a substantial economic burden, with many patients also reporting chronic fatigue. Gut bacterial profiles in IBS differ from those in health, but prebiotics, probiotics and synbiotics have shown limited benefit and poor durable colonisation. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of undigested carbohydrates and fibre, fuel colonic epithelial cells and influence motility, visceral sensitivity, immune activity and gut barrier function. Since faecal SCFA composition in IBS differs from health, the authors examine, using faecal microbiota transplantation (FMT) data, whether individual SCFAs, rather than dysbiosis generally, are mechanistically linked to IBS symptoms and fatigue.
Study Design
This narrative mini-review draws mainly on pooled data from a single-centre FMT programme in which IBS patients received either 60 g donor faeces (active) or their own faeces (control). Faecal total SCFA, acetic, propionic and butyric acid concentrations were measured by gas chromatography at baseline, one month, one year, two years and three years, and correlated with IBS-SSS, the Birmingham IBS Symptom Questionnaire, and the Fatigue Assessment Scale (FAS). The review also incorporates two supplementation trials: a multicentre study of microencapsulated sodium butyrate in adults, and a randomised placebo-controlled trial of calcium butyrate in children. No new statistical testing was performed.
Patient Population
The FMT cohort comprised adults with IBS followed over three years, split between donor-faeces and own-faeces groups. Chronic fatigue, assessed separately in a cited cross-sectional analysis, was reported in 54.5% of IBS patients. Demographic and subtype details were not reported in the mini-review, though butyric acid responses did not differ by IBS subtype across the FMT programme or the two supplementation trials.
Key Findings
In the FMT group, butyric acid rose from 17% of total faecal SCFAs at baseline to 23% at one month, 22% at one year, and 33% at two and three years, while acetic acid fell from 64% to 50-51% and propionic acid fell from 19% to 16-17%. Controls (own faeces) showed stable proportions throughout (butyric acid 15-18%). Faecal butyric acid was inversely related to IBS-SSS and Birmingham questionnaire scores (including pain, diarrhoea and constipation subitems) and to FAS physical and mental fatigue scores. Acetic and propionic acid showed no relationship with symptoms and did not differ between responders and non-responders at two and three years. The adult trial found twelve weeks of microencapsulated sodium butyrate improved symptoms without changing microbiota composition; the paediatric trial found calcium butyrate reduced symptoms versus placebo, accompanied by microbiota changes.
Discussion
Butyric acid is proposed as the SCFA most plausibly linked to symptom generation, acting via serotonin, peptide YY and glucagon-like peptide-1 in enterochromaffin and L-cells, affecting visceral sensitivity, gastric emptying and transit. A more speculative link involving inflammation and the Human antigen R pathway may connect butyric acid to both IBS and fatigue, alongside unproven supplements such as resveratrol, β-hydroxy-β-methyl butyric acid and tributyrin. Neither butyrate trial reported adverse events.
Authors’ Conclusions
Acetic and propionic acid appear uninvolved in IBS symptoms, whereas butyric acid appears significant via serotonin, peptide YY and GLP-1 modulation. Capsule-form sodium butyrate is considered a promising therapy, potentially enabling patients to adopt a fibre-rich diet once symptoms are controlled. The mechanisms linking butyric acid to chronic fatigue remain unclear, warranting further study.
Reference
El-Salhy M, Shin CM, Kim YS, Hatlebakk JG. Possible roles of short-chain fatty acids in the pathophysiology and treatment of irritable bowel syndrome. World J Transl Med. 2026;12(3):122740. doi:10.5528/wjtm.122740
This Scientific Publication Summary is an objective summary of the published trial for personal and educational use. It does not constitute clinical advice, endorsement of the intervention, or a recommendation to alter clinical practice.