Microbiome-driven IBS metabotypes influence response to the low FODMAP diet: Insights from the faecal volatome
Description
WORKING GROUP Thomas Edward Conley 1,2, Rachael Slater 1, Stephen Moss 3,4, David Bulmer 5, Juan de la Revilla Negro 3, Umer Zeeshan Ijaz 6, David Mark Pritchard 1,2, Miles Parkes 3,4, Chris Probert 1,2 1. University of Liverpool Institute of Systems, Molecular and Integrative Biology, Liverpool, UK 2. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK 3. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 4. University of Cambridge Department of Medicine, Gastroenterology and Hepatology, Cambridge, Cambridgeshire, UK 5. University of Cambridge Department of Pharmacology, Cambridge, Cambridgeshire, UK 6. University of Glasgow, Mazumdar-Shaw Advanced Research Centre, Glasgow, UK 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). INTERPREATATION 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. Enclosed: 1. Master table containing clinical & faecal SPME-GC-MS data. 2. File containing correlation coefficients between VOCs & bacterial pathways.