MULTISPECIES PROBIOTICS ABOLISH ACUTE PANCREATITIS-ASSOCIATED MUCOSAL BARRIER FAILURE IN MURINE ILEUM

Abstract

Intestinal mucosal barrier failure during acute pancreatitis is associated with translocation of luminal bacteria to extra-intestinal sites. Resulting infectious complications are a major cause of morbidity and mortality. Aim of this study was to determine if multispecies probiotics can diminish mucosal barrier failure in the course of experimental acute pancreatitis (AP). Mice were treated daily with a mixture of six probiotic strains (Ecologic 641®, Winclove BioIndustries, Amsterdam, The Netherlands, 2.5×109 bacteria/oral gavage) or placebo, from 2 days prior to cerulein induced AP (hourly intraperitoneal injections, 50μg/kg, for 10 hours) until termination 72 hours after the first injection. Sham procedure consisted of 10 hourly sterile saline injections, without probiotic or placebo treatment. Mucosal barrier function of the distal ileum was assessed by measurement of mucosal integrity (electrical resistance, R: Ω.cm2) and permeability (steady state transepithelial flux of 0.01 gr/l Na-fluorescin, flux: ng/cm2/h) at 36°C, in Ussing chambers. AP reduced mucosal integrity and increased permeability (AP (n = 13) vs. sham (n = 15): R = 28.1 ± 1.4 Ω.cm2 (mean ± SEM) vs. 37,5 ± 1.7, P = 0.002; flux = 400 ± 48 ng/cm2/h vs. 189 ± 18, P = 0.001, ANOVA). Probiotic treatment completely abolished the AP-induced mucosal barrier failure (placebo vs. probiotics (n = 15): R = 26.4 ± 2.6 vs. 34.9 ± 1.8, P = 0.003; flux = 427 ± 62 vs. 246 ± 32, P = 0.014). Mucosal resistance and permeability of probiotic treated mice were not different from those of healthy controls or sham (P = 0.551 and P = 0.194, respectively). Conclusions: Experimental acute pancreatitis results in decreased integrity and increased permeability of ileal mucosa. This mucosal barrier failure can be abolished by the used regime of selected multispecies probiotics. Support of mucosal barrier function by multispecies probiotics may provide a novel strategy to reduce infectious complications during acute pancreatitis.