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

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 (p FWEcorrected < 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.

Editorial: meal‐induced symptoms in irritable bowel syndrome—“all in the mind”?

“…Wu et al present a randomised, double-blind, cross-over trial in which fructans, glucose, or saline were instilled into the stomach of IBS patients and healthy controls. 7 The findings demonstrate altered brain, but not gut, responses in IBS. Fructans, but not glucose or saline, increased small bowel motility and colonic gas production to a similar extent in both study groups.…”

“…Wu et al present a randomised, double‐blind, cross‐over trial in which fructans, glucose, or saline were instilled into the stomach of IBS patients and healthy controls 7 . The findings demonstrate altered brain, but not gut, responses in IBS.…”

Long‐term personalized low FODMAP diet in IBS

“…However, the exact cause of visceral hypersensitivity has not been elucidated yet, even though central and peripheral sensitization, allodynia and hyperalgesia, together with psychological factors have been implicated in its genesis 7 . Indeed, it has been recently shown by fMRI that brains of IBS patients respond differently to fructan infusion in areas related to pain, such as the cerebellum, supramarginal gyrus, anterior and midcingulate cortex, insula and thalamus, highlighting the importance of a dysfunctional gut‐brain axis in IBS 45 . Among peripheral factors, low‐grade inflammation and increased levels of neuroimmune mediators, including histamine, tryptase, trypsin, proteases, and prostaglandins, have been suggested to play a role 46,47 .…”

“…7 Indeed, it has been recently shown by fMRI that brains of IBS patients respond differently to fructan infusion in areas related to pain, such as the cerebellum, supramarginal gyrus, anterior and midcingulate cortex, insula and thalamus, highlighting the importance of a dysfunctional gut-brain axis in IBS. 45 Among peripheral factors, low-grade inflammation and increased levels of neuroimmune mediators, including histamine, tryptase, trypsin, proteases, and prostaglandins, have been suggested to play a role. 46,47 Enteroendocrine cells have also been implicated in the genesis of IBS symptoms, as dietary guidance and restricting poorly fermented carbohydrates modify colonic chromogranin A, PYY, and serotonin cell density.…”

Letter: gut–brain axis dysfunction underlies symptom generation in irritable bowel syndrome—a plea for rational interpretation of irrational doses of FODMAPs. Authors' reply

“…We appreciate the opportunity to discuss the methods and interpretation of our recent paper, 1 offered by the letter of Drs Halmos and Gibson, 2 raising problems with the translatability of high doses of fructans (i.e. exceeding normal daily dietary intake) used in mechanistic research to real life.…”