Microbiome-driven IBS metabotypes influence response to the low FODMAP diet: insights from the faecal volatome



Conley, Thomas Edward, Slater, Rachael ORCID: 0000-0001-9765-6978, Moss, Stephen, Bulmer, David Colin, Negro, Juan de la Revilla, Ijaz, Umer Zeeshan, Pritchard, David Mark ORCID: 0000-0001-7971-3561, Parkes, Miles and Probert, Chris ORCID: 0000-0003-0477-6714
(2024) Microbiome-driven IBS metabotypes influence response to the low FODMAP diet: insights from the faecal volatome EBIOMEDICINE, 107. 105282-. ISSN 2352-3964, 2352-3964

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Abstract

Background: Irritable bowel syndrome (IBS) is a common and debilitating disorder manifesting with abdominal pain and bowel dysfunction. A mainstay of treatment is dietary modification, including restriction of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). A greater response to a low FODMAP diet has been reported in those with a distinct IBS microbiome termed IBS-P. We investigated whether this is linked to specific changes in the metabolome in IBS-P. Methods: Solid phase microextraction gas chromatography-mass spectrometry was used to examine the faecal headspace of 56 IBS cases (each paired with a non-IBS household control) at baseline, and after four-weeks of a low FODMAP diet (39 pairs). 50% cases had the IBS-P microbial subtype, while the others had a microbiome that more resembled healthy controls (termed IBS-H). Clinical response to restriction of FODMAPs was measured with the IBS-symptom severity scale, from which a pain sub score was calculated. Findings: Two distinct metabotypes were identified and mapped onto the microbial subtypes. IBS-P was characterised by a fermentative metabolic profile rich in short chain fatty acids (SCFAs). After FODMAP restriction significant reductions in SCFAs were observed in IBS-P. SCFA levels did not change significantly in the IBS-H group. The magnitude of pain and overall symptom improvement were significantly greater in IBS-P compared to IBS-H (p = 0.016 and p = 0.026, respectively). Using just five metabolites, a biomarker model could predict microbial subtype with accuracy (AUROC 0.797, sensitivity 78.6% (95% CI: 0.78–0.94), specificity 71.4% (95% CI: 0.55–0.88). Interpretation: A metabotype high in SCFAs can be manipulated by restricting fermentable carbohydrate, and is associated with an enhanced clinical response to this dietary restriction. This implies that SCFAs harbour pro-nociceptive potential when produced in a specific IBS niche. By ascertaining metabotype, microbial subtype can be predicted with accuracy. This could allow targeted FODMAP restriction in those seemingly primed to respond best. Funding: This research was co-funded by Addenbrooke's Charitable Trust, Cambridge University Hospitals and the Wellcome Sanger Institute, and supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).

Item Type: Article
Uncontrolled Keywords: Irritable bowel syndrome, Low FODMAP diet, Metabolome, Metabotype, Microbiome, Short chain fatty acids, Volatile organic compounds
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 15 Oct 2024 14:57
Last Modified: 22 May 2026 15:10
DOI: 10.1016/j.ebiom.2024.105282
Open Access URL: https://doi.org/10.1016/j.ebiom.2024.105282
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3185101
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