TY - JOUR T1 - α-Haemolysin of <em>Escherichia coli</em> in IBD: a potentiator of inflammatory activity in the colon JF - Gut JO - Gut SP - 1893 LP - 1901 DO - 10.1136/gutjnl-2013-306099 VL - 63 IS - 12 AU - Roland Bücker AU - Emanuel Schulz AU - Dorothee Günzel AU - Christian Bojarski AU - In-Fah M Lee AU - Lena J John AU - Stephanie Wiegand AU - Traute Janßen AU - Lothar H Wieler AU - Ulrich Dobrindt AU - Lothar Beutin AU - Christa Ewers AU - Michael Fromm AU - Britta Siegmund AU - Hanno Troeger AU - Jörg-Dieter Schulzke Y1 - 2014/12/01 UR - http://gut.bmj.com/content/63/12/1893.abstract N2 - Objective α-Haemolysin (HlyA) influences host cell ionic homeostasis and causes concentration-dependent cell lysis. As a consequence, HlyA-producing Escherichia coli is capable of inducing ‘focal leaks’ in colon epithelia, through which bacteria and antigens translocate. This study addressed the role of HlyA as a virulence factor in the pathogenesis of colitis according to the ‘leaky gut’ concept. Design To study the action of HlyA in the colon, we performed oral administration of HlyA-expressing E coli-536 and its isogenic α-haemolysin-deficient mutant (HDM) in three mouse models: wild type, interleukin-10 knockout mice (IL-10−/−) and monoassociated mice. Electrophysiological properties of the colonised colon were characterised in Ussing experiments. Inflammation scores were evaluated and focal leaks in the colon were assessed by confocal laser-scanning microscopy. HlyA quantity in human colon biopsies was measured by quantitative PCR. Results All three experimental mouse models infected with HlyA-producing E coli-536 showed an increase in focal leak area compared with HDM. This was associated with a decrease in transepithelial electrical resistance and an increase in macromolecule uptake. As a consequence, inflammatory activity index was increased to a higher degree in inflammation-prone mice. Mucosal samples from human colon were E coli HlyA-positive in 19 of 22 patients with ulcerative colitis, 9 of 9 patients with Crohn's disease and 9 of 12 healthy controls. Moreover, focal leaks were found together with 10-fold increased levels of HlyA in active ulcerative colitis. Conclusions E coli HlyA impairs intestinal barrier function via focal leak induction in the epithelium, thereby intensifying antigen uptake and triggering intestinal inflammation in vulnerable mouse models. Therefore, HlyA-expressing E coli strains should be considered as potential cofactors in the pathogenesis of intestinal inflammation. ER -