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Neurogastroenterology
Original research
Changes in signalling from faecal neuroactive metabolites following dietary modulation of IBS pain
  1. Caroline J Tuck1,2,
  2. Amal Abu Omar2,3,
  3. Giada De Palma4,
  4. Samira Osman2,
  5. Nestor N Jiménez-Vargas2,
  6. Yang Yu2,
  7. Sean MP Bennet2,
  8. Cintya Lopez-Lopez2,
  9. Josue O Jaramillo-Polanco2,
  10. Corey C Baker2,
  11. Aidan SW Bennett2,
  12. Mabel Guzman-Rodriguez2,
  13. Quentin Tsang2,
  14. Taylor Alward2,
  15. Sebastien Rolland5,
  16. Celine Morissette2,
  17. Elena F Verdu4,
  18. Premysl Bercik4,
  19. Stephen J Vanner2,
  20. Alan E Lomax2,
  21. David E Reed2
  1. 1 Department of Sport, Exercise and Nutrition Sciences, La Trobe University, Melbourne, Victoria, Australia
  2. 2 Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
  3. 3 Department of Physiology, Jordan University of Science and Technology, Irbid, Jordan
  4. 4 Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  5. 5 Department of Medicine, Hopital Maisonneuve-Rosemont, Montreal, Québec, Canada
  1. Correspondence to Dr David E Reed, Gastroinestinal Diseases Research Unit, Queen's University, Kingston, ON K7L 3N6, Canada; david.reed{at}queensu.ca

Abstract

Objective Dietary therapies for irritable bowel syndrome (IBS) have received increasing interest but predicting which patients will benefit remains a challenge due to a lack of mechanistic insight. We recently found evidence of a role for the microbiota in dietary modulation of pain signalling in a humanised mouse model of IBS. This randomised cross-over study aimed to test the hypothesis that pain relief following reduced consumption of fermentable carbohydrates is the result of changes in luminal neuroactive metabolites.

Design IBS (Rome IV) participants underwent four trial periods: two non-intervention periods, followed by a diet low (LFD) and high in fermentable carbohydrates for 3 weeks each. At the end of each period, participants completed questionnaires and provided stool. The effects of faecal supernatants (FS) collected before (IBS FS) and after a LFD (LFD FS) on nociceptive afferent neurons were assessed in mice using patch-clamp and ex vivo colonic afferent nerve recording techniques.

Results Total IBS symptom severity score and abdominal pain were reduced by the LFD (N=25; p<0.01). Excitability of neurons was increased in response to IBS FS, but this effect was reduced (p<0.01) with LFD FS from pain-responders. IBS FS from pain-responders increased mechanosensitivity of nociceptive afferent nerve axons (p<0.001), an effect lost following LFD FS administration (p=NS) or when IBS FS was administered in the presence of antagonists of histamine receptors or protease inhibitors.

Conclusions In a subset of IBS patients with improvement in abdominal pain following a LFD, there is a decrease in pronociceptive signalling from FS, suggesting that changes in luminal mediators may contribute to symptom response.

  • irritable bowel syndrome
  • abdominal pain
  • diet
  • neurogastroenterology
  • nerve - gut interactions

Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.

https://doi.org/10.1136/gutjnl-2022-327260

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    Data availability statement

    Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.

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    Footnotes

    • CJT and AAO are joint first authors.

    • AEL and DER are joint senior authors.

    • Twitter @tuck_caroline

    • Contributors CJT, AAO, SR, SJV, AEL and DER designed of the study. CJT, CM, SJV and DER conducted the clinical study. CJT analysed the clinical data. CJT, SO, NNJ-V, SMPB, CL-L, JOJ-P, YY and TA conducted the patch clamp recordings. AAO, ASWB, CCB and QT conducted the ex vivo afferent nerve recordings. GDP, EFV and PB analysed the microbiota. SMPB analysed the metabolomics. NNJ-V and MG-R conducted the histamine and proteolytic measurements in FS. CJT, AAO, SJV, AEL and DER wrote the paper. All authors approved the final manuscript. Article guarantor: DER.

    • Funding This work was supported by an American Gastroenterological Association-Allergan Foundation Pilot Research Award in Irritable Bowel Syndrome. This work was also supported by the IMAGINE (Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects)- SPOR (Strategy for Patient Oriented Research) initiative of Canadian Institutes of Health Research (CIHR) and the Weston Family Microbiota Initiative. CJT was supported by a fellowship from the CIHR Institute of Nutrition, Metabolism and Diabetes, the Canadian Nutrition Society and Nestle Health Sciences (funding reference number CNU-158242). AAO was supported by Jordan University of Science and Technology. SJV, DER, GDP, PB, EF and AEL were also supported by CIHR operating grants.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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