Human breast milk-derived exosomes may help maintain intestinal epithelial barrier integrity
Human breast milk-derived exosomes may help maintain intestinal epithelial barrier integrity
复制标题
人母乳来源的外泌体可能有助于维持肠上皮屏障的完整性
DOI：
10.1038/s41390-021-01449-y
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发表时间：
2021-03-17
影响因子：
3.6
通讯作者：
Zhu, Xueping
中科院分区：
文献类型：
--
作者：
He, Shan;Liu, Gang;Zhu, Xueping
背景本研究探讨了人母乳来源的exosomes在体内和体外的功能。体外分析分为五组：（1）未添加试剂的对照，（2）添加外泌体，（3）用脂多糖（LPS）刺激，（4）用外泌体预处理并用LPS刺激，和（5）用无外泌体的HBM预处理并用LPS刺激。对于体内分析，将小鼠幼仔随机分配至四组：（1）母乳喂养的幼仔的对照组，（2）坏死性小肠结肠炎诱导（NEC）的幼仔，（3）在NEC诱导前6小时用HBM衍生的外来体预处理的幼仔，和（4）在NEC诱导前6小时用无外来体的HBM预处理的幼仔。和occludin在组3和5中降低。在动物模型中，第3组中的小鼠幼仔显示出比第2组或第4组中的小鼠幼仔更轻的肠组织损伤，并且具有比第2组和第4组更低的促炎细胞因子水平和更高的上皮紧密连接蛋白水平。结论HBM衍生的外泌体通过减少对肠上皮的炎症和损伤以及通过恢复肠紧密连接蛋白而在预防NEC中发挥有益作用。本研究试图（1）分析早产或足月分娩的母亲的母乳（HBM）之间是否存在外泌体水平的差异，以及（2）调查这些外泌体是否可以帮助维持肠上皮紧密连接蛋白ZO-1，claudin-1，和闭合素在体外和体内的NEC的存在下。
BackgroundThis study explores the functions of exosomes derived from human breast milk (HBM) in vivo and in vitro.MethodsHBM-derived exosomes were collected from healthy lactating mothers. In vitro analysis were divided into five groups: (1) a control with no added agents, (2) exosomes added, (3) stimulated with lipopolysaccharide (LPS), (4) pretreated with exosomes and stimulated with LPS, and (5) pretreated with exosome-free HBM and stimulated with LPS. For in vivo analysis, mouse pups were randomly assigned to four groups: (1) a control group of breastfed pups, (2) necrotizing enterocolitis-induced (NEC) pups, (3) pups pretreated with HBM-derived exosomes 6 h before being induced by NEC, and (4) pups pretreated with exosome-free HBM 6 h before NEC induction.ResultsExpression of zonula occludens-1 (ZO-1), claudin-1, and occludin were decreased in groups 3 and 5. In the animal model, mice pups in group 3 showed milder intestinal tissue injury than those in group 2 or 4 and had lower levels of the proinflammatory cytokines and higher levels of epithelial tight-junction proteins than groups 2 and 4.ConclusionsHBM-derived exosomes exert beneficial effects in preventing NEC by reducing inflammation and injury to the intestinal epithelium as well as by restoring intestinal tight-junction proteins.ImpactHBM-derived exosomes can help protect the epithelial tight-junction proteins ZO-1, claudin, and occludin from inflammatory attack.This study sought (1) to analyze whether there were differences in exosome levels between the human breast milk (HBM) of mothers who had delivered preterm or at term and (2) to investigate whether these exosomes could help sustain the intestinal epithelial tight-junction proteins ZO-1, claudin-1, and occludin in the presence of NEC in vitro and in vivo.