A103 PROBIOTIC FORMULATIONS DIFFERENTIALLY AFFECT DISEASE OUTCOME IN A MOUSE MODEL OF NECROTIZING ENTEROCOLITIS

Abstract

Abstract Background Necrotizing enterocolitis (NEC) causes severe gastrointestinal disease in premature infants. A precise etiology is not yet known, but it is generally agreed that intestinal immaturity & alterations in the gut microbiota play key roles in NEC progression. There is growing interest in the clinical use of probiotics for the prevention of NEC in at-risk infants. Some probiotics, which are defined as beneficial bioactive microbes that provide a health benefit when administered in sufficient amounts, may influence disease outcome in premature infants with NEC. Aims To investigate the efficacy of two commercially available probiotic formulations, Lacidofil® and ProBiokid®, in the prevention of experimentally-induced NEC. Methods At gestational day 12.5, treated dams were administered probiotics (109 cfu/mL) in drinking water (Table 1). NEC was induced at postnatal day 5 or when pups were ≥ 3.0 g by the administration of hyperosmolar formula, hypoxia, and lipopolysaccharide (4 mg/kg). NEC pups receiving probiotics were administered 108cfu in hyperosmolar formula once daily during the morning feeding. Body weight, survival and disease severity were scored. Results Neither probiotic intervention affected overall survival of NEC-induced pups. Control dam-fed pups (NN) continued to gain weight as expected over time, while untreated NEC pups (NNNEC) exhibited a significant delay in weight gain. LLNEC pups exhibited the greatest percent body weight increase over time, possibly due to a lower birth weight. Lacidofil administration did not improve NEC-induced tissue damage irrespective of the timing of intervention. In contrast, Probiokid provided to both dam and pups (PPNEC) resulted in less severe tissue damage compared to their control counterparts. Conclusions These finding demonstrate strain-specific differences in two different commercial probiotic formulations in the prevention of NEC in newborn mice. Future studies seek to provide insight into how Lacidofil and Probiokid engage intestinal stem cells (Lgr5-GFP mice), cell proliferation (Ki67 positivity) and differentiation (MUC2 & Chromogranin A positivity) in the NEC-damaged intestine. Funding Agencies CIHRMITACS Accelerate Postdoctoral Award