How Does Human Milk Protect Against Necrotizing Enterocolitis (NEC)? Targeted Validation and Time-Course Analysis of 35 Gene Responses as NEC-Signature in Fetal Intestinal Epithelial Cells
3
Issued Date
2022-08-01
Resource Type
ISSN
15362310
eISSN
15578100
Scopus ID
2-s2.0-85136339206
Pubmed ID
35900271
Journal Title
OMICS A Journal of Integrative Biology
Volume
26
Issue
8
Start Page
440
End Page
450
Rights Holder(s)
SCOPUS
Bibliographic Citation
OMICS A Journal of Integrative Biology Vol.26 No.8 (2022) , 440-450
Suggested Citation
Tongviratskool C., Pongsakul N., Kanaprach P., Supapannachart S., Nuntnarumit P., Chutipongtanate S. How Does Human Milk Protect Against Necrotizing Enterocolitis (NEC)? Targeted Validation and Time-Course Analysis of 35 Gene Responses as NEC-Signature in Fetal Intestinal Epithelial Cells. OMICS A Journal of Integrative Biology Vol.26 No.8 (2022) , 440-450. 450. doi:10.1089/omi.2022.0075 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83649
Title
How Does Human Milk Protect Against Necrotizing Enterocolitis (NEC)? Targeted Validation and Time-Course Analysis of 35 Gene Responses as NEC-Signature in Fetal Intestinal Epithelial Cells
Other Contributor(s)
Abstract
Breastfeeding reduces the risk of necrotizing enterocolitis (NEC), one of the most common causes of morbidity and mortality in preterm infants. However, the molecular substrates by which human milk (HM) offers protection against NEC are not well known. Using fetal intestinal epithelial cells treated with known NEC aggravators, namely lipopolysaccharide (LPS) and platelet-activating factor (PAF), we mapped the time-course of changes in targeted expression analysis of 35 NEC-associated genes, so-called the NEC signature. We found, first, that HM treatment fully rescued LPS/PAF-induced fetal intestinal cell death at 12 and 24 h (n = 5). Differential gene expression and bioinformatics revealed that HM did not mitigate inflammatory and cell death signals, but instead promoted cell proliferation and stress response pathways to mitigate LPS/PAF-induced inflammatory cell death. From this, epidermal growth factor (EGF) synthesis emerged as the central player in rescue of the fetal intestinal cell death. Functional validation was supported by reversal of the cellular rescue by HM following EGF knockdown by small interfering RNA. In conclusion, this study suggests that HM might offer protection against NEC through enhancing intestinal EGF production to rescue the inflammatory cell death. Future studies are warranted to verify these HM molecular protective effects in NEC models in vivo. The findings reported herein also support future research avenues to discover new therapeutics to boost intrinsic EGF production in the injured intestinal tissues in neonates with NEC, for example, by bioactive components in human milk, natural compounds, or small molecules.