Abstract and Introduction
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 (Q 2 0.296 vs. randomised −0.175) predicted clinical response.
Conclusions: Baseline faecal and urine metabolites may predict response to the LFD.
Introduction
Irritable bowel syndrome is a chronic and debilitating functional gastrointestinal (GI) disorder characterised by abdominal pain and altered bowel habit, affecting 1.5%–4.1% of adults globally.[1]
Altered microbiota and faecal metabolites are part of the pathophysiology of IBS however it is unclear if the changes are a cause or feature of IBS. In a systematic review of 24 studies, Enterobacteriaceae, Lactobacillaceae (family), and Bacteroides (genus) were shown to be higher in IBS than healthy controls, whereas Clostridiales, Faecalibacterium, Bifidobacterium (genus), and Faecalibacterium prausnitzii (species) were shown to be lower.[2] Altered microbiota and short-chain fatty acid (SCFA) production in IBS may contribute to low-grade inflammation,[3,4] altered tight junction protein arrangement and increased jejunal humoral immunity described in diarrhoea-predominant IBS (IBS-D).[5,6]
A major approach to dietary management of IBS is the restriction of fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs), termed the low FODMAP diet (LFD),[7] which significantly reduces IBS severity, abdominal pain, overall symptoms and improves bowel habits and quality of life.[8,9] A systematic review including 22 studies identified that the rate of dichotomous clinical response (measured as either >50-point reduction in IBS-SSS score or adequate symptom relief) to the LFD was 61%–69% meaning that 31%–39% of patients that follow the diet will not respond.[8]
The LFD is burdensome to follow, requiring complete dietary change. It may reduce intake of fibre, calcium and iron and decrease diet quality,[10,11] and reduce faecal bifidobacteria concentration and faecal butyrate.[12] Bifidobacteria are considered beneficial for gastrointestinal health due to regulating colonic pH, favourable immune modulation and pathogen exclusion,[13,14] and butyrate contributes to colonocyte epithelial integrity.[13] Therefore, due to the burden for patients in following the LFD and the potential disturbance to the gastrointestinal ecosystem, there would be a significant benefit to both patients and healthcare providers if symptom response to the LFD could be predicted.
A range of biological markers of response to LFD have been proposed. A commercial 'dysbiosis test' has shown conflicting results for individual microbial species in predicting response to the LFD, with one study finding higher Actinobacter and Streptococcus at baseline in responders[15] and another showing that these were both lower in responders at baseline.[16] Volatile organic compounds (VOCs) are intermediaries/endpoints of metabolic pathways that reflect many aspects of colonic metabolism.[17–19] Faecal VOC profiles were demonstrated to differ between responders and non-responders to the LFD,[20] however, individual metabolites were not characterised and specific response-predicting metabolites have yet to be identified.
The current study explores differences in faecal microbiota, and faecal and urine metabolites, between responders and non-responders to the LFD in IBS using data from the previously published 3-arm parallel, placebo-controlled trial. The original paper compared endpoints between the different dietary interventions[12] and these are not described here.
Aliment Pharmacol Ther. 2023;58(4):404-416. © 2023 Blackwell Publishing
