PWE-126 Low fodmap diet effect on IBS gastrointestinal microbiome and metabolites and prediction of response

Introduction Prebiotic β-galactooligosaccharides (B-GOS) may counteract the microbiome modifying effect of the low FODMAP diet (LFD) in patients with irritable bowel syndrome (IBS). Faecal metabolites may predict why only some patients respond to the LFD paving the way towards more personalised treatment. The aim of this randomised controlled trial (RCT) was to investigate: a) the impact of the LFD and LFD+1.4 g/d B-GOS compared to Control on the gut microbiome in IBS, and b) if differences in faecal or urinary metabolites predict response to the LFD. Methods A 3-arm RCT was performed in 69 IBS patients randomised to: Sham diet +Placebo (Control), LFD +Placebo (LFD) or LFD +B GOS. This study investigated global symptom response (adequate relief), gut microbiome (16S rRNA sequencing), short-chain fatty acids (SCFA, gas liquid chromatography), volatile organic compounds (VOC) (gas chromatography/mass spectrometry) and urine metabolomics (NMR spectroscopy) at baseline (BL) and 4 weeks. Data were analysed by Chi 2 for dichotomous outcomes and Kruskal-WallisMann-Whitney U tests for continuous variables. Predictive analysis was tested using receiver operator curves (ROC) and orthoganol partial least squared discriminant analysis (OPLS-DA). Results Response rate (adequate relief) at 4 weeks was greater in the LFD+GOS (67%) and LFD (50%) than the Control group (30%) (p=0.046). The phylum Actinobacteria was lower (p Bifidobacterium (p=0.002) and Collinsella (p=0.004), in the LFD and LFD+B GOS groups compared to Control at 4 weeks. Prediction of response to the LFD was seen in the LFD group only, with significant separation of BL faecal VOC profiles (AUC=0.854, p=0.045), faecal propionate (AUC=0.848, p=0.009), and urine metabolite profiles (Q 2 =0.296 vs randomised-0.175). Roseburia, Blautia, Lachnospira and Faecalibacterium, were positively but not significantly associated with VOC classes that predicted response when all samples were correlated. Microbiome and VOC showed a significant negative correlation between propionic acid derivatives and Phascolarctobacterium (r=-0.85 and-0.81, p Phascolarctobacterium between responders (1.5%) and non-responders (9.3%) at BL did not reach significance (p=0.055). Conclusions The LFD +B GOS improves symptoms in IBS compared to Control but the LFD significantly reduces Actinobacteria and addition of 1.4 g/d of prebiotic B-GOS does not overcome this effect. Faecal VOCs and SCFAs and urine metabolomes may predict clinical response to the LFD, and specific bacterial groups correlate with predictive metabolites. Larger studies are required to validate these algorithms to develop personalised nutrition in IBS.