0442

EVALUATION OF ORGANIC ACIDS INDUCED INTESTINAL MUCOSAL INJURY IN NEWBORN RATS AS AN ANIMAL MODEL FOR NEONATAL NECROTIZING ENTEROCOLITIS

Lin J^1,2, Nafday SM², Magid MS², Holzman IR² and Babyatsky MW²

¹ The YuYing Children’s Hospital of Wenzhou Medical College, Wenzhou, China

² Department of Pediatrics, Mount Sinai School of Medicine, New York, USA

Objective: Role of organic acids such as short chain fatty acids (SCFAs) and lactic acid (LA) in the pathogenesis of neonatal necrotizing enterocolitis (NEC) remains to be elucidated. The purpose of this study was to test the hypothesis that luminal administration of organic acids can induce reproducible intestinal injury in newborn rats, which can be used as an animal model for NEC.

Method: A total of 72 Sprague-Dawley rats (10 days old) were randomly divided into 7 different groups. A 3.5F umbilical catheter was rectally inserted 3.5 to 4 cm deep into the proximal colon and each group of rats received one of the following organic acid solutions at a volume of 0.1 ml/10gm body weight. Acetic acid (AA), butyric acid (BA) and LA at two different concentrations (150 mM and 300 mM) were used in the experiments. The pH of all solutions was adjusted to 4.0. Normal saline (NS) with pH adjusted to 4.0 was used as control. Animals were housed with their mothers before and after the experiments. After 24 hours, all rats were sacrificed and the daily weight change, 3 cm proximal colon wet weight and a modified histological injury score done by two pathologist who were blind to the group assignment were used to compare the difference among each groups.

Results: Both AA and BA at 300 mM induced severe mucosal injury in the colon and a moderate mucosal injury in the distal ileum as evidenced by impaired weight gain, increased colon wet weight and increased histological injury scores (p<0.01, ANOVA). Both AA and BA at 150 mM induced a mild mucosal injury in the colon only. Surprisingly, the LA at 150 or 300 mM with pH 4.0 did not induce any identifiable intestinal mucosal injury. The daily weight gain and the colon wet weight were comparable to that of NS control group (p>0.05).

Conclusions: We conclude that luminal administration of AA or BA but not LA can induce dose-dependent intestinal mucosal injury in newborn rats, which resemble the pathology seen in NEC patients. Overproduction/accumulation of SCFAs in the proximal colon may play a major role in the pathogenesis of NEC in premature infants. The beneficial effect of LA-producing probiotics in pathogenesis of NEC may be, in part, due to the production of lactic acid, which is much less injurious than AA and BA, two of the main SCFAs.