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Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Inhibiting Intestinal Damage via Increasing the Proliferation of Crypt Cells
Author(s) -
Wang Chenyuan,
Zhang Ming,
Guo Huiyuan,
Yan Jingyu,
Liu Fan,
Chen Jianliang,
Li Yiran,
Ren Fazheng
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900262
Subject(s) - necrotizing enterocolitis , crypt , ileum , organoid , tlr4 , enterocolitis , lgr5 , stem cell , intestinal mucosa , intestinal epithelium , biology , immunology , medicine , andrology , endocrinology , inflammation , epithelium , pathology , microbiology and biotechnology , cancer stem cell
Scope Necrotizing enterocolitis (NEC) is a devastating disease that is highly lethal in premature infants. Human milk oligosaccharides (HMOs) efficiently reduce the incidence of NEC. However, the protective mechanism of HMO treatment is unknown. It is hypothesized that HMOs protect against NEC by inhibiting the damage to intestinal epithelial cells. Methods and results C57BL/6 pups are challenged with hypoxia and cold stress to induce NEC. All pups are sacrificed after 72 h. It is found that HMO administration reduces the concentrations of IL‐8 in the serum and ileum of all NEC mice. Ileum toll‐like receptor 4 (TLR4) protein expression and nuclear factor kappa‐B (NFκB) pathway activation are inhibited. The proliferative ability of enterocytes in the ileum is restored as determined by labeling with proliferation markers (Ki67, SOX9). In a 3D culture intestinal crypt organoids study, HMO treatment improves the maturation of organoid cells and increases the ratio of proliferative cells under lipopolysaccharides (LPS) treatment. HMO treatment downregulates TLR4 expression in the organoid cells, thus reducing the effect of LPS. Conclusion HMOs protect intestinal epithelial cells from injury by accelerating the turnover of crypt cells by reducing the expression of TLR4 on intestinal epithelial cells.