The human milk oligosaccharides (HMO) present in breast milk block the binding of Gram-negative bacteria to the complex of TLR4 and MD2 by competitive inhibition, thus blocking the activation of TLR4 and preventing NEC. Formula does not contain HMO. Thus Gram-negative bacteria can bind to the TLR4-MD2 complex, (1) activating NF-κB that leads to cell death, and (2) increases the expression of TLR4 in the cell membrane.1
Reference
Sodhi, C. P. et al. The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr. Res. https://doi.org/10.1038/s41390-020-0852-3 (2020).
Acknowledgements
D.J.H. is supported by R01GM078238 and R01DK083752 from the National Institutes of Health, and this research was funded in part by a Sponsored Research Grant to D.J.H. from Abbott Nutrition.
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Sodhi, C.P., Wipf, P., Yamaguchi, Y. et al. Insights image for “The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling.”. Pediatr Res 89, 248 (2021). https://doi.org/10.1038/s41390-020-01184-w
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DOI: https://doi.org/10.1038/s41390-020-01184-w
