TY - JOUR T1 - Two microbiota subtypes identified in Irritable Bowel Syndrome with distinct responses to the low-FODMAP diet JF - bioRxiv DO - 10.1101/2021.05.14.444142 SP - 2021.05.14.444142 AU - Kevin Vervier AU - Stephen Moss AU - Nitin Kumar AU - Anne Adoum AU - Meg Barne AU - Hilary Browne AU - Arthur Kaser AU - Chris Kiely AU - Anne Neville AU - Nina Powell AU - Tim Raine AU - Mark D. Stares AU - Ana Zhu AU - Juan De La Revilla Negro AU - Trevor Lawley AU - Miles Parkes Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/14/2021.05.14.444142.abstract N2 - 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 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 normalization of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBSP subjects compared to 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 exclusion 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.Significance of this studyWhat is already known on this subject?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?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?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 IBSP 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.Competing Interest StatementTR has received research/educational grants and/or speaker/consultation fees from Abbvie, Arena, AstraZeneca, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda and UCB. SM has received research/educational grants and/or speaker/consultation fees from Abbvie. MP has received research/educational grants and/or speaker/consultation fees from Takeda. TDL is the co-founder and CSO of Microbiotica. ER -