Antibacterial and anti-inflammatory effects of Lactobacillus reuteri in its biofilm state contribute to its beneficial effects in a rat model of experimental necrotizing enterocolitis

Abstract

IntroductionNecrotizing enterocolitis (NEC) remains a significant surgical emergency in neonates. We have demonstrated the efficacy of Lactobacillus reuteri (Lr) in protecting against experimental NEC when administered as a biofilm by incubation with maltose loaded dextranomer microspheres. Lr possesses antimicrobial and anti-inflammatory properties. We developed mutant strains of Lr to examine the importance of its antimicrobial and anti-inflammatory properties in protecting the intestines from NEC. MethodsPremature rat pups were exposed to hypoxia/hypothermia/hypertonic feeds to induce NEC. To examine the importance of antimicrobial reuterin and anti-inflammatory histamine, pups received either native or mutant forms of Lr, in either its planktonic or biofilm states, prior to induction of NEC. Intestinal histology was examined upon sacrifice. ResultsCompared to no treatment, administration of a single dose of Lr in its biofilm state significantly decreased the incidence of NEC (67% vs. 18%, p < 0.0001), whereas Lr in its planktonic state had no significant effect. Administration of reuterin-deficient or histamine-deficient forms of Lr, in either planktonic or biofilm states, resulted in significant loss of efficacy. ConclusionAntimicrobial and anti-inflammatory effects of Lr contribute to its beneficial effects against NEC. This suggests that both infectious and inflammatory components contribute to the etiology of NEC.