Tu1439 Fecal Cysteine Protease Activity in Patients With Irritable Bowel Syndrome -Clinical and Physiological Aspects.

Abstract

Increased activity of fecal proteases has been reported in patients with irritable bowel syndrome (IBS). Animal studies demonstrated that fecal proteases induce physiological alterations in intestinal motility, sensation and permeability, similar to those found in patients with IBS. Fecal cysteine-protease has been suggested to have a role in the pathogenesis of C-IBS. However, fecal cysteine-protease has not been investigated in other subtypes of IBS and its relationship with IBS symptoms and intestinal physiology is unknown. Aims: To measure and compare the level of fecal cysteine-protease activity (FCPA) between patients with IBS, subtypes of IBS, and healthy controls and to investigate the relationship between FCPA, abdominal pain, IBS severity and gastrointestinal transit. Methods: We studied a total of 60 patients who met the Rome III criteria for IBS (C-IBS, n=14; D-IBS, n=28; MIBS, n=18) and 34 healthy controls. FCPA was measured in homogenized fecal samples of all subjects using an enzymatic-based method with specific substrates and inhibitors, and expressed as Δfluo/mg protein. Abdominal pain was assessed using a 0-10 scale and IBS severity scores was assessed by IBS-Symptom Severity Scale. Wireless Motility Capsule (SmartPillTM) was used to measure small bowel (SBTT), colonic (CTT), and whole gut (WGTT) transit times. Comparisons of FCPA between the groups of interest were done using student t-tests. Pearson correlation analysis was used to assess the association between FCPA and clinical and physiological variables. Results: Compared to HC, subjects with IBS, and all subtypes of IBS, had significantly higher levels of FCPA (HC: 128.0±334.4; all IBS: 595.9±853.1, p=0.03; D-IBS: 447.4±635.2, p=0.014; M-IBS: 749.9±748.5, p<0.0001; CIBS: 694.8±1281.2, p=0.02 respectively). Subjects with C-IBS had significantly higher FCPA levels than D-IBS (p<0.0001). FCPA levels showed a significant positive correlation with abdominal pain (r=0.37, p=0.006) and a trend of a positive correlation with IBS symptom severity (r=0.24, p=0.08). No correlation was found between FCPA levels and the transit time variables of interest. Demographic characteristics were similar between the groups. Conclusions: We provide evidence for significant differences in FCPA between patients with IBS, subtypes of IBS and healthy controls. FCPA is strongly correlated with abdominal pain, a hallmark symptom of IBS. These findings suggest a role for luminal cysteine protease in the pathogenesis of IBS.