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

Kevin Vervier, Stephen Moss, Nitin Kumar, Anne Adoum, Meg Barne, Hilary Browne, Arthur Kaser, Chris Kiely, B Anne Neville, Nina Powell, Tim Raine, Mark D. Stares, Ana Zhu, Juan De La Revilla Negro, Trevor Lawley, Miles Parkes
doi: https://doi.org/10.1101/2021.05.14.444142
Kevin Vervier
1The Wellcome Trust Sanger Institute
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  • For correspondence: kv4@sanger.ac.uk
Stephen Moss
2Addenbrooke’s Hospital
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Nitin Kumar
3Wellcome Trust Sanger Institute
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Anne Adoum
3Wellcome Trust Sanger Institute
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Meg Barne
2Addenbrooke’s Hospital
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Hilary Browne
4Wellcome Sanger Institute
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Arthur Kaser
2Addenbrooke’s Hospital
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Chris Kiely
5Royal North Shore Hospital
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B Anne Neville
3Wellcome Trust Sanger Institute
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Nina Powell
2Addenbrooke’s Hospital
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Tim Raine
2Addenbrooke’s Hospital
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Mark D. Stares
3Wellcome Trust Sanger Institute
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Ana Zhu
3Wellcome Trust Sanger Institute
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Juan De La Revilla Negro
2Addenbrooke’s Hospital
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Trevor Lawley
3Wellcome Trust Sanger Institute
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Miles Parkes
2Addenbrooke’s Hospital
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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 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 study

What 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 Statement

TR 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.

Footnotes

  • ↵(*) co first author

  • ↵(**) co last author

  • Fix some naming typos Fix keywords

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 16, 2021.
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Two microbiota subtypes identified in Irritable Bowel Syndrome with distinct responses to the low FODMAP diet
Kevin Vervier, Stephen Moss, Nitin Kumar, Anne Adoum, Meg Barne, Hilary Browne, Arthur Kaser, Chris Kiely, B Anne Neville, Nina Powell, Tim Raine, Mark D. Stares, Ana Zhu, Juan De La Revilla Negro, Trevor Lawley, Miles Parkes
bioRxiv 2021.05.14.444142; doi: https://doi.org/10.1101/2021.05.14.444142
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Two microbiota subtypes identified in Irritable Bowel Syndrome with distinct responses to the low FODMAP diet
Kevin Vervier, Stephen Moss, Nitin Kumar, Anne Adoum, Meg Barne, Hilary Browne, Arthur Kaser, Chris Kiely, B Anne Neville, Nina Powell, Tim Raine, Mark D. Stares, Ana Zhu, Juan De La Revilla Negro, Trevor Lawley, Miles Parkes
bioRxiv 2021.05.14.444142; doi: https://doi.org/10.1101/2021.05.14.444142

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