Introduction Patients with IBS-D have been reported to have increased faecal serine protease activity which could induce visceral hypersensitivity and increase gut permeability by activating proteinase activated receptor-2 (PAR-2). These proteases could be either endogenous (pancreatic or mast cell) or bacterial in origin.
Aim To define the type and origin of proteases using a proteomic method.
Methods Study 1: Serine protease activity in stool supernatant from 36 patients meeting the Rome III criteria for IBS-D and 9 healthy controls was evaluated using a previous published method.1 Patients completed a one week stool diary and a hospital anxiety and depression score. Study 2: Serine proteases from a subset of 8 pooled patient samples were purified using a combination of affinity chromatography and SDS-PAGE. Protease identification using proteolysis and mass-spectrometry was performed. Study 3: Assessment of stool amylase and elastase was performed using two commercially available ELISAs.
Results Study 1: Serine protease activity was significantly increased in patients, 621 ± 94 versus 211 ± 46 units of trypsin/mg protein in controls, p = 0.04. Serine protease activity was significantly correlated with anxiety r = 0.5 p = 0.002. Study 2: The predominant proteases were pancreatic in origin including trypsin, elastase and carboxypeptidase-B. Additionally there was abundant pancreatic amylase. Study 3: Stool amylase but not elastase was significantly increased in IBS-D 183 ± 35 103 units/ml versus controls 78 ± 44. Amylase also correlated with serine protease activity, r = 0.33, p < 0.05.
Conclusion We confirm previous reports of increased serine proteases in IBS-D but these appear to be of pancreatic origin and associated with increased anxiety. Anxiety may cause rapid transit which reduces degradation by colonic bacteria and increases fecal protease.
- faecal elastase
- feacal amylase
- irritable bowel syndrome
- serine proteases
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Competing interests K. Garsed: None Declared, G. Singh: None Declared, D. Tooth: None Declared, C. Lam: None Declared, R. Banwait: None Declared, M. Lingaya: None Declared, R. Spiller Grant / Research Support from: Norgine, Consultant for: Boehringer, Alberio.
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