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

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_{FWE-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.