Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.

Visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction and low-grade inflammation in a subset of irritable bowel syndrome patients

“…Unlike previous studies, no strong correlations between the severity of symptoms and experimental parameters were found in our study (Zhou et al, 2009), indicating that the mechanisms involved in the expression of symptoms are still complicated and inadequately understood. A strength of our study was that our analysis excluded the confounding effects of mental factors.…”

“…In this study, we confirmed that D-IBS patients have somatic hypersensitivity using both cold and ischemic sensitivity tests. Our results were similar to those of previous studies (Zhou et al, 2009;. To our knowledge, our work is the first study to use diverse methods, especially the ischemic sensitivity test, to examine somatic sensitivity in China.…”

“…Although the pathophysiology of IBS is unclear, visceral hypersensitivity is one of the accepted mechanisms, and may have some relationships with the severity of the symptoms (Zhou et al, 2009). However, previous evaluations of visceral sensitivity have typically been based on "rapid phasic distension", and Harraf et al (1998) claimed that visceral hypersensitivity could not be induced by the "ascending method of limits (AML)" protocol.…”

Mechanisms of Stress-induced Visceral Pain

“…128,129 In a series of pivotal studies, Zhou and coworkers determined the importance of miR-29 on visceral hypersensitivity via a mechanism involving increased intestinal permeability. 34,130,131 Increased expression of mi-R-29a and miR29b were associated with increased intestinal permeability in mice following stress exposure. In support of a role miR-29 they employed Mir29 -/-mice and discovered that stress-induced intestinal permeability was significantly attenuated via a mechanism involving regulation of Claudin-1 mRNA expression.…”

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

“…Single-nucleotide polymorphisms in CDH1 , which encodes the tight junction protein E-cadherin, are associated with increased risk of post-infectious IBS ( 40 ). Detailed molecular studies of the epithelial barrier indicate the expression and subcellular distribution of tight junction proteins are substantially altered in IBS patients ( 41 -44 ), and impaired intestinal permeability has been shown to correlate with pain / discomfort and / or bowel habit ( Table 1 ) ( 34,37,41,43 ). However, impaired barrier defenses are unlikely to directly cause pain, but instead ease access of luminal contents to the GI wall, promoting infl ammatory responses and modulating sensory-motor function.…”