Summary Background Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. Aims To assess intestinal permeability at different sites of the GI tract in different subtypes of well‐characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. Methods IBS patients and HC underwent a multi‐sugar test to assess site‐specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0–5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0–24 h and 5–24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Results Ninety‐one IBS patients, i.e. 37% IBS‐D, 23% IBS‐C, 33% IBS‐M and 7% IBS‐U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS‐C and IBS‐D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS‐D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0–24 and 5–24 h sucralose/erythritol ratio between groups. Conclusions Small intestinal permeability is increased in patients with IBS‐D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS.

Apart from more severe symptomatology, hypersensitive IBS patients are characterized by significantly younger age compared with normosensitive IBS patients. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT00702026).

In this placebo-controlled trial in IBS patients with visceral hypersensitivity, no significant effect of a multispecies probiotic on viscerperception was observed. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT00702026).

Optimal cutoff for visceral hypersensitivity was found at pressure 26 mmHg with a VAS ≥20 mm, resulting in 63.5% of IBS patients being hypersensitive and 11% being allodynic. Standardization of barostat procedures and defining optimal cutoff values for hypersensitivity is warranted when employing rectal barostat measurements for research or clinical purposes.

SUMMARY BackgroundAlterations in serotonin (5-HT) metabolism have been postulated to play a role in the pathogenesis of irritable bowel syndrome (IBS). However, previous reports regarding 5-HT metabolism in IBS are contradicting.

Alterations in the modulatory balance of pro- and antinociceptive central processing of noxious peripheral input may serve as in integrative hypothesis for explaining visceral hypersensitivity in IBS. Nevertheless, it remains troublesome to estimate the contribution of central and peripheral factors in visceral hypersensitivity, posing a challenge in determining effective therapeutic entities.

Increased transcription of TRPV1 may provide a possible explanation for pain generation in IBS. While the neuropeptides SP and somatostatin were both found to be increased in IBS, these changes are not sufficient to explain pain generation. Pain generation in IBS is probably explained by a complex redundancy in the regulation of local nociceptive mechanisms, which remains a subject of intensive investigation.

Our findings do not support a role for the biological processes as ascertained by biomarkers in visceral hypersensitivity in IBS patients. This study is registered in the US National Library of Medicine (clinicaltrials.gov, NCT00775060).