Aliment Pharmacol Ther. 2023 Aug;58(4):404-416.doi: 10.1111/apt.17609. Epub 2023 Jun 14.

Bridgette Wilson ^1 2, Tokuwa Kanno ³, Rachael Slater ⁴, Megan Rossi ¹, Peter M Irving ^5 6, Miranda C Lomer ^1 2, Chris Probert ⁴, A James Mason ³, Kevin Whelan ¹

Author information

¹Department of Nutritional Sciences, King's College London, London, UK.

²Department of Nutrition and Dietetics, Guys and St Thomas' NHS Foundation Trust, London, UK.

³King's College London, Institute of Pharmaceutical Science, London, UK.

⁴University of Liverpool, Institute of Systems, Molecular and Integrative Biology, Liverpool, UK.

⁵Department of Gastroenterology, Guys and St Thomas' NHS Foundation Trust, London, UK.

⁶School of Immunology and Microbial Sciences, King's College London, London, UK.

Abstract

Background: The low FODMAP diet (LFD) leads to clinical response in 50%-80% of patients with irritable bowel syndrome (IBS). It is unclear why only some patients respond.

Aims: To determine if differences in baseline faecal microbiota or faecal and urine metabolite profiles may separate clinical responders to the diet from non-responders allowing predictive algorithms to be proposed.

Methods: We recruited adults fulfilling Rome III criteria for IBS to a blinded randomised controlled trial. Patients were randomised to sham diet with a placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.8 g/d B-galactooligosaccharide (LFD/B-GOS), for 4 weeks. Clinical response was defined as adequate symptom relief at 4 weeks after the intervention (global symptom question). Differences between responders and non-responders in faecal microbiota (FISH, 16S rRNA sequencing) and faecal (gas-liquid chromatography, gas-chromatography mass-spectrometry) and urine (¹ H NMR) metabolites were analysed.

Results: At 4 weeks, clinical response differed across the 3groups with adequate symptom relief of 30% (7/23) in controls, 50% (11/22) in the LFD group and 67% (16/24) in the LFD/B-GOS group (p = 0.048). In the control and the LFD/B-GOS groups, microbiota and metabolites did not separate responders from non-responders. In the LFD group, higher baseline faecal propionate (sensitivity 91%, specificity 89%) and cyclohexanecarboxylic acid esters (sensitivity 80%, specificity 78%), and urine metabolite profile (Q² 0.296 vs. randomised -0.175) predicted clinical response.

Conclusions: Baseline faecal and urine metabolites may predict response to the LFD.