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

Abstract

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. To unravel the mechanisms underlying FODMAP-induced symptom reporting, we investigated gut and brain responses to fructan administration in IBS patients and HC. This randomised, double-blind, cross-over study consisted of three visits where fructans (40g/500mL saline), glucose (40g/500mL saline) or saline (500mL) were infused intragastrically during 1h MR brain scanning; abdominal MRI was performed before, 1h, and 2h post-infusion. Symptoms were rated using validated scales. 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. 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.