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Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome

Wu, J; Masuy, I; Biesiekierski, JR; Fitzke, HE; Parikh, C; Schofield, L; Shaikh, H; ... Van Oudenhove, L; + view all (2022) Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome. Alimentary Pharmacology and Therapeutics , 55 (6) pp. 670-682. 10.1111/apt.16812. Green open access

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Abstract

Background: FODMAPs produce similar small bowel water and colonic gas in patients with irritable bowel syndrome (IBS) and healthy controls (HCs), despite IBS patients reporting increased gastrointestinal (GI) symptoms. Aim: To unravel the mechanisms underlying FODMAP-induced symptom reporting, we investigated gut and brain responses to fructan administration in IBS patients and HC. Methods: This randomised, double-blind, cross-over study consisted of three visits where fructans (40 g/500 mL saline), glucose (40 g/500 mL saline) or saline (500 mL) were infused intragastrically during 1 h MR brain scanning; abdominal MRI was performed before, 1 h, and 2 h post-infusion. Symptoms were rated using validated scales. Results: In IBS (n = 13), fructans induced more cramps, pain, flatulence and nausea compared to glucose (P = 0.03, 0.001, 0.009 and <0.001 respectively), contrary to HC (n = 13) (all P > 0.14), with between-group differences for cramps and nausea (P = 0.004 and 0.023). Fructans increased small bowel motility and ascending colonic gas and volume equally in IBS and HC (between-group P > 0.25). The difference in colonic gas between fructans and saline covaried with differences in bloating and cramps in IBS (P = 0.008 and 0.035 respectively). Pain-related brain regions responded differentially to fructans in IBS compared to HC, including the cerebellum, supramarginal gyrus, anterior and midcingulate cortex, insula and thalamus (pFWE-corrected < 0.05); these brain responses covaried with symptom responses in IBS. Conclusions: Fructans increase small bowel motility and colon gas and volume similarly in IBS patients and HC. Increased symptom responses to fructans in IBS covary with altered brain responses in pain-related regions, indicating that gut-brain axis dysregulation may drive FODMAP-induced symptom generation in IBS.

Type: Article
Title: Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/apt.16812
Publisher version: https://doi.org/10.1111/apt.16812
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, Pharmacology & Pharmacy, abdominal imaging, FODMAP, irritable bowel syndrome, FUNCTIONAL GASTROINTESTINAL DISORDERS, VISCERAL SENSITIVITY, LACTOSE-INTOLERANCE, GAS-PRODUCTION, DIET LOW, DISTENSION, PAIN, MECHANISMS, EFFICACY, DIARRHEA
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10147199
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