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.

Self-Reported Food Triggers and Food Fears Impact Nutrient Intake and Quality of Life in Patients with Irritable Bowel Syndrome and Functional Dyspepsia

“…Several mechanistic studies have shown that colonic hypersensitivity to luminal distension, rather than excessive fermentation of FODMAPs, underlie symptom generation in IBS patients. 39 , 40 This perspective supports the notion that addressing food-related anxiety and hypersensitivity mechanisms may be equally, if not more, important than dietary eliminations.…”

Self-Reported Food Triggers and Food Fears Impact Nutrient Intake and Quality of Life in Patients with Irritable Bowel Syndrome and Functional Dyspepsia

“…Several mechanistic studies have shown that colonic hypersensitivity to luminal distension, rather than excessive fermentation of FODMAPs, underlie symptom generation in IBS patients. 39 , 40 This perspective supports the notion that addressing food-related anxiety and hypersensitivity mechanisms may be equally, if not more, important than dietary eliminations.…”

The low FODMAP diet in clinical practice: where are we and what are the long-term considerations?

“…The vagus nerve connects the enteric nervous system and the central nervous system, which is often referred to as the gut-brain axis. Recent mechanistic work looking at pain receptors in the brain show that fructans increase signalling in the pain-related areas of the brain supporting the theory that IBS is a dysfunction of the gut-brain axis (19) .…”

Variability in stool symptoms in youth with abdominal pain‐associated disorders of gut–brain interaction

“…This has been demonstrated in studies examining pain in response to mechanical rectal stretch with greater reported pain in those with IBS versus normal healthy controls 11 . Increased activity in the pain centers of the brain has been demonstrated in people with IBS when compared to healthy controls in response to the same instigated small bowel motility, colon gas, and volume change 12 . It is feasible that decreased pain with a stool is indicative of rectal hypersensitivity to stretch, and that increased pain is related to dysregulated motility and spasms.…”

Self-Reported Food Triggers and Food Fears Impact Nutrient Intake and Quality of Life in Patients with Irritable Bowel Syndrome and Functional Dyspepsia

“…Several mechanistic studies have shown that colonic hypersensitivity to luminal distension, rather than excessive fermentation of FODMAPs, underlie symptom generation in IBS patients. 39 , 40 This perspective supports the notion that addressing food-related anxiety and hypersensitivity mechanisms may be equally, if not more, important than dietary eliminations.…”

The low FODMAP diet in clinical practice: where are we and what are the long-term considerations?

“…The vagus nerve connects the enteric nervous system and the central nervous system, which is often referred to as the gut-brain axis. Recent mechanistic work looking at pain receptors in the brain show that fructans increase signalling in the pain-related areas of the brain supporting the theory that IBS is a dysfunction of the gut-brain axis (19) .…”

Variability in stool symptoms in youth with abdominal pain‐associated disorders of gut–brain interaction

“…This has been demonstrated in studies examining pain in response to mechanical rectal stretch with greater reported pain in those with IBS versus normal healthy controls 11 . Increased activity in the pain centers of the brain has been demonstrated in people with IBS when compared to healthy controls in response to the same instigated small bowel motility, colon gas, and volume change 12 . It is feasible that decreased pain with a stool is indicative of rectal hypersensitivity to stretch, and that increased pain is related to dysregulated motility and spasms.…”

Self-Reported Food Triggers and Food Fears Impact Nutrient Intake and Quality of Life in Patients with Irritable Bowel Syndrome and Functional Dyspepsia

“…Several mechanistic studies have shown that colonic hypersensitivity to luminal distension, rather than excessive fermentation of FODMAPs, underlie symptom generation in IBS patients. 39 , 40 This perspective supports the notion that addressing food-related anxiety and hypersensitivity mechanisms may be equally, if not more, important than dietary eliminations.…”

The low FODMAP diet in clinical practice: where are we and what are the long-term considerations?

“…The vagus nerve connects the enteric nervous system and the central nervous system, which is often referred to as the gut-brain axis. Recent mechanistic work looking at pain receptors in the brain show that fructans increase signalling in the pain-related areas of the brain supporting the theory that IBS is a dysfunction of the gut-brain axis (19) .…”

Variability in stool symptoms in youth with abdominal pain‐associated disorders of gut–brain interaction

“…This has been demonstrated in studies examining pain in response to mechanical rectal stretch with greater reported pain in those with IBS versus normal healthy controls 11 . Increased activity in the pain centers of the brain has been demonstrated in people with IBS when compared to healthy controls in response to the same instigated small bowel motility, colon gas, and volume change 12 . It is feasible that decreased pain with a stool is indicative of rectal hypersensitivity to stretch, and that increased pain is related to dysregulated motility and spasms.…”