(P07-033-23) The Intra-Amniotic Administration- an Emerging Method To Investigate Necrotizing Enterocolitis, In Vivo (Gallus gallus)

Objectives: Demonstrate necrotizing enterocolitis (NEC) in a novel in vivo (Gallus gallus) model through intra-amniotic administration with dextran sodium sulfate (DSS, demonstrated agent to induce NEC) to induce NEC pathology, significant pathophysiology, and negative bacterial-host interactions within a premature gastrointestinal system.

Methods: On incubation day 17, broiler chicken (Gallus gallus) viable embryos were injected intra-amniotically with 1 mL DSS in DI H₂O. Four treatment groups (0.1%, 0.25%, 0.5%, 0.75%, 1%, 1.25% and 1.5% DSS) and two controls (H₂O/non-injected controls) were administered. Upon hatch, blood, cecum, small intestine, and liver were collected for assessment of hemoglobin and intestinal permeability, intestinal microbiota alterations, intestinal morphometric assessment, and mRNA gene expression of relevant of nutrient transporter and inflammatory proteins, respectively.

Results: Our results reveal that with DSS exposure, intestinal permeability was significantly increased, and negative intestinal morphological changes were found. In the 0.50% and 0.75% DSS groups, villus surface area and goblet cell diameter was significantly decreased (p > 0.05). Furthermore, there was a significant (p > 0.05) increase in pathogenic bacterial abundance (E. coli and Klebsiella) in the 0.75% DSS group compared to the controls, demonstrating cecal microbiota dysbiosis. However, at the higher induction rate the intestinal villi recovered dramatically. Taken together, our results demonstrate striking similarities between our observations in the Gallus gallus model compared with NEC patients.

Conclusions: This study is the first to demonstrate NEC symptoms through intra-amniotic administration of DSS in vivo (Gallus gallus), whereas previous studies have utilized rodent and pig models. The results of this study are promising evidence to investigate increased concentrations of DSS further to cause more severe NEC symptoms and identify potential novel biomarkers of less severe NEC cases.

Funding Sources: No external funding was utilized for the study.