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

Aliment Pharmacol Ther. 2022 Mar;55(6):670-682. doi: 10.1111/apt.16812. Epub 2022 Feb 15.

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.

Trial registration: ClinicalTrials.gov NCT04283487.

Keywords: FODMAP; abdominal imaging; irritable bowel syndrome.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Gut Axis
  • Cross-Over Studies
  • Flatulence / etiology
  • Fructans
  • Glucose
  • Humans
  • Irritable Bowel Syndrome* / diagnosis
  • Muscle Cramp
  • Nausea
  • Pain

Substances

  • Fructans
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT04283487