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

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.

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.

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.

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.

A faecal metabotype enriched in SCFAs associated with an IBS-D phenotype characterised by pain, urgency, rapid transit and higher stool frequency.