Abstract

Due to an increasing incidence of necrotizing enterocolitis (NEC), as well as its associated mortality and long-term complications seen in surviving patients, the main focus of research in NEC has shifted to the prevention and treatment of the disease. The hypothesis of this work is that the strain Lactobacillus salivarius LPLM-O1 can decrease the intestinal injuries in a model of induced NEC. 26 newborn Sprague-Dawley pups were used in this study and randomized in three groups: control group (n = 6), which were fed with infant formula (Similac NeosureTM, Abbott); probiotic group (n = 10), which were fed with the same infant formula but fortified with 109 colony-forming units (CFU) of Lactobacillus salivarius LPLM-O1, and the NEC-induced group (n = 10). Each group was fed with 100 μl of food formula every three hours, using a modified syringe. The probiotic and NEC groups were exposed to asphyxia- and cold-induced stress to develop experimental NEC. At the end of the experiment (96 hrs), animals were sacrificed, and their small intestines were carefully removed and evaluated for typical signs of NEC, microbiological count and histological analyses. The histological analysis of the NEC-induced group showed transmural necrosis (grade 4); in the probiotic group, the grade was comparatively lower (grade 2). Survival ratewas higher in the probiotic group (83%) than in the NEC-induced group (46%); however, the difference in not statistically significant (p = 0.14). Lactic acid bacteria counts were higher in the probiotic group than in the NEC-induced group (8.4 × 108 and 6.1 × 107 CFU/intestine tissue gram, respectively). According to these results, the model of artificial induction of NEC was effectively establishedin all pups, and the probiotic strain slightly decreases the injuries’ grade in newborn pups.

Highlights

  • Necrotizing enterocolitis (NEC) is an extremely catastrophic and common gastrointestinal disease acquired by very low birth weight infants (VLBW, with birth weight being under 1.5 kg)

  • Several animal models have been used in the study of NEC, such as acute intestinal injury models, where the injuries are induced by intravascular administration of platelet-activating factors (PAF), on young adult rats [4] and mice [5]

  • Julling et al (2006) developed a neonatal model of NEC in mice, in which newborn mice were obtained by Caesarea and exposed to formula feeding and stress by hypoxia-cold [6]

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Summary

Introduction

Necrotizing enterocolitis (NEC) is an extremely catastrophic and common gastrointestinal disease acquired by very low birth weight infants (VLBW, with birth weight being under 1.5 kg). Developing reliable animal models that can be reproduced for studying NEC remains a key part of the attempts to determine its main causes. In this context, studies based on surgical procedures in infants with NEC have shown limited value, as the extirpated tissue samples usually show necrosis and non-specific inflammatory changes; they are not useful for studying the early events leading to NEC. A neonatal model of NEC on caesarean-born, formula-fed mice that were daily exposed to stress by hypoxia has been developed [6]. Caesarean-section is linked to a high mortality in newborn mice that are not related to NEC

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