TitleProteomics analysis reveals digestion-resistant proteins from colostrum are associated with inflammatory and cytotoxic responses in intestinal epithelial cells.
Publication TypeJournal Article
Year of Publication2021
AuthorsChen, Y, Kim, BJin, Dallas, DC
JournalJPEN J Parenter Enteral Nutr
Date Published10/2021

BACKGROUND: Although human-milk feeding reduces the risk of necrotizing enterocolitis (NEC) in preterm infants compared with formula feeding, the exact risk-reduction mechanism remains unknown. As NEC occurs at the distal small intestine in which digestion has occurred, we applied proteomics to examine the extent to which colostrum proteins survive simulated infant in vitro-digestion and, thus, have potential to exert biological function.

METHODS: Ten preterm colostrum samples were left undigested or in vitro-digested, and lipopolysaccharide (LPS)-binding protein, soluble cluster of differentiation 14, and tumor necrosis factor (TNF) receptors I and II were measured using enzyme-linked immunosorbent assay in all undigested and in vitro-digested samples. Fully differentiated Caco-2 cells were exposed to digested colostrum samples before stimulation with LPS or TNF or no stimulation. Inflammation (interleukin-8) and cytotoxicity (lactate dehydrogenase) were measured. Proteomic analyses of undigested and in vitro-digested samples were done using mass spectrometry.

RESULTS: We found that most proteins in colostrum are significantly, if not completely, degraded after in vitro-digestion. We found select individual and combination digestion-resistant proteins that were positively correlated with LPS- and TNF-induced inflammation.

CONCLUSION: These results indicate the importance of considering the extent to which specific dietary compounds survive digestion to reach their site of claimed action (distal intestine) and that some digestion-resistant proteins may be contributing toward "low-grade" inflammation that is necessary to promote intestinal growth and maturation during early infancy. This work provides the most detailed understanding of human-milk protein degradation with simulated infant in vitro-digestion to date.

Alternate JournalJPEN J Parenter Enteral Nutr
PubMed ID34687453
Grant ListW4002 / / USDA Multistate Workgroup /
K99/R00 / / USDA Multistate Workgroup /
R00HD079561 / / Pathway to Independence Career Award, Eunice Kennedy Shriver Institute of Child Health & Development of the National Institutes of Health /
2018-67017-27521 / / USDA National Institute of Food and Agriculture /
2017-1586 / / Gerber Foundation /
/ / International Society for Research on Human Milk and Lactation-Family Larsson-Rosenquist Foundation Trainee Expansion Program /