Two microbiota subtypes identified in Irritable Bowel Syndrome with distinct responses to the low-FODMAP diet

Abstract

ABSTRACT Objective Reducing FODMAPs can be clinically beneficial in IBS but the mechanism is poorly 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 normalization of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBS P subjects compared to 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 exclusion 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. Significance of this study What is already known on this subject? IBS subjects often respond to a low FODMAP diet. The gut microbiota has been implicated in IBS. The microbiota in IBS subjects may change with diet. What are the new findings? We were able to stratify patients with IBS according to their gut microbiota species and metabolic gene signatures. We identified a distinct gut microbiota subtype with an enhanced clinical response to a low FODMAP diet compared to other IBS subjects. How might it impact on clinical practice in the foreseeable future? The potential development of a microbiota signature as a biomarker to manage IBS cases with a low FODMAP diet recommendation. If the bacteria represented in the IBS P subtype are shown to play a pathogenic role in IBS, perhaps through the metabolic activity this provides a target for new therapies and an intermediate phenotype by which to assess them.