HUMAN BREAST MILK PROTECTS FROM INTESTINAL EPITHELIAL NECROSIS IN A "NEC IN A DISH" MODEL IN MICE
Maame Efua Sampah*, Andres J. Gonzalez Salazar, Mark L. Kovler, Chhinder P. Sodhi, Hongpeng Jia, Peng Lu, William B. Fulton, Yukihiro Yamaguchi, Sanxia Wang, Thomas Prindle, David Hackam
Department of Surgery, Johns Hopkins Medicine, Baltimore, MD
Introduction
Necrotizing enterocolitis (NEC) results from an abnormal response to the microbiome of the premature gut. It has been previously shown that the metabolic stress of infant formula feeding leads to polarization of the immune system towards an inflammatory state which contributes to NEC. However, the entire signaling pathway leading to an exacerbated inflammatory response and mechanisms to reverse the inflammation are not completely understood. We have previously shown that human milk oligosaccharides, key components of breast milk prevent NEC by inhibition of TLR4 signaling.
Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. In this study, we made use of a mouse enteroid model system to demonstrate that human milk modulates the NEC pathogenesis by reducing necrosis.
Methods
Primary stem cell-derived small intestinal enteroids obtained from neonatal mice were treated with human breast milk. NEC in a dish was developed by culturing enteroids on cover slips in the presence of bacteria obtained from the intestine of babies diagnosed with NEC. Culture components were assessed for expression of necrotic markers as a readout for NEC.
Results
In control cells, there was no necrosis, whereas treatment with NEC bacteria induced significant necrosis similar to that seen in human and experimental NEC. strikingly, treatment with mouse breast milk, significantly reduced the expression of the necrotic markers.
Conclusion
Our study demonstrates a protective effect of breast milk on necrosis in cells of epithelial lineage in this study performed using enteroids derived from neonatal mice or premature human small intestine. This suggests a novel mechanism for the protective effect of breast milk in NEC pathogenesis.
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