Abstract
OBJECTIVE: Reducing FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) can be clinically beneficial in IBS but the mechanism is incompletely understood. We aimed to detect microbial signatures that might predict response to the low FODMAP diet and assess whether microbiota compositional and functional shifts could provide insights into its mode of action. DESIGN: We used metagenomics to determine high-resolution taxonomic and functional profiles of the stool microbiota from IBS cases and household controls (n=56 pairs) on their usual diet. Clinical response and microbiota changes were studied in 41 pairs after 4 weeks on a low FODMAP diet. RESULTS: Unsupervised analysis of baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBS(P) (pathogenic-like) and IBS(H) (health-like) subtypes. IBS(P) microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species. IBS(H) microbiomes were similar to controls. On the low FODMAP diet, IBS(H) and control microbiota were unaffected, but the IBS(P) signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalisation of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBS(P) subjects compared with IBS(H) (p=0.02). CONCLUSION: 50% of IBS cases manifested a 'pathogenic' gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBS(P) cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP reduction in IBS(P) may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBS(P) species and metabolic pathways might yield insights regarding IBS pathogenic mechanisms.