The Emerging Short Chain Fatty Acid Enriched Metabotype in Irritable Bowel Syndrome and Its Potential Clinical Relevance

Conley, TE, Duncan, A, Modasia, A, Ford, AC, Pritchard, DM ORCID: 0000-0001-7971-3561, Hildebrand, F, Warren, FJ, Spiller, R and Probert, CS ORCID: 0000-0003-0477-6714 (2026) The Emerging Short Chain Fatty Acid Enriched Metabotype in Irritable Bowel Syndrome and Its Potential Clinical Relevance ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 64 (2). pp. 208-221. ISSN 0269-2813, 1365-2036

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Abstract

Background: Metabolomic analysis in irritable bowel syndrome (IBS) has identified metabotypes enriched in faecal short-chain fatty acids (SCFAs), but it remains unclear whether this reflects rapid colonic transit or if these metabolites actively contribute to pathophysiology. Aims: We aimed to determine whether an SCFA metabotype could be identified within a cohort of patients with moderate–severe IBS-D and assess whether this metabotype associated with greater clinical severity, alterations in gut transit time and specific microbiome features. Methods: This was a post hoc cross-sectional exploratory analysis of baseline data from the multicentre, randomised, placebo-controlled trial of ondansetron in IBS-D (TRITON: ISRCTN17508514). Faecal volatile organic compounds were profiled by GC–MS. The microbiome was characterised by whole-genome shotgun metagenomic sequencing. Unsupervised hierarchical clustering was used to identify an SCFA-enriched metabotype and non-negative matrix factorisation (NMF) enabled the derivation of complementary metabosignatures by assessing continuous gradients in metabolite composition. Results: A SCFA-enriched metabotype was identified in 20/63 participants (31.7%). This metabotype was associated with more severe abdominal pain, urgency, increased stool frequency and faster whole-gut transit. NMF identified three metabosignatures: S3 was typified by a high proportion of SCFAs and captured the SCFA-enriched metabotype, while S1 and S2 corresponded to the non-SCFA (“Other”) metabotype. SCFA relative abundance positively correlated with symptom severity and inversely correlated with transit time. The Other metabotype and S1/S2 signatures were enriched in taxa linked to slower transit, whereas S3 showed no overlapping taxa with the SCFA metabotype. Conclusion: A faecal metabotype enriched in SCFAs associated with an IBS-D phenotype characterised by pain, urgency, rapid transit and higher stool frequency.

Item Type:	Article
Uncontrolled Keywords:	irritable bowel syndrome, metabolome, metabotype, volatile organic compounds
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology (T&R Staff) Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Molecular & Clinical Cancer Medicine
Depositing User:	Symplectic Admin
Date Deposited:	01 May 2026 16:04
Last Modified:	23 Jul 2026 20:54
DOI:	10.1111/apt.70677
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3198282
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