Chenyuan Wang1,2, Ming Zhang3, Huiyuan Guo1,2, Jingyu Yan4, Fan Liu1, Jianliang Chen2, Yiran Li2, Fazheng Ren1,2. 1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China. 2. Key Laboratory of Functional Dairy, China Agricultural University, Beijing, 100083, China. 3. School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing, 100048, China. 4. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116011, China.
Abstract
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.
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.
Authors: Ilse H de Lange; Charlotte van Gorp; Laurens D Eeftinck Schattenkerk; Wim G van Gemert; Joep P M Derikx; Tim G A M Wolfs Journal: Nutrients Date: 2021-05-19 Impact factor: 5.717
Authors: Laura E Carr; Misty D Virmani; Fernanda Rosa; Daniel Munblit; Katelin S Matazel; Ahmed A Elolimy; Laxmi Yeruva Journal: Front Immunol Date: 2021-02-12 Impact factor: 7.561