Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet

Kevin Vervier ,1 Stephen Moss,2,3 Nitin Kumar,1 Anne Adoum,1 Meg Barne,4Hilary Browne,1 Arthur Kaser,3,5 Christopher J Kiely,6 B Anne Neville,1 Nina Powell,4Tim Raine ,2,7 Mark D Stares,1 Ana Zhu,1 Juan De La Revilla Negro,2Trevor D Lawley,1 Miles Parkes 2,3

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 IBSP (pathogenic-like) and IBSH (health-like) subtypes. IBSP microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species.
IBSH microbiomes were similar to controls. On the low FODMAP diet, IBSH and control microbiota were unaffected, but the IBSP 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 IBSP subjects compared with IBSH (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 IBSP cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP reduction in IBSP may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBSP species and metabolic pathways might
yield insights regarding IBS pathogenic mechanisms.