Gao Runnan, Huang Yingying, Li Bo, Zhang Rong, Lee Carol, Alganabi Mashriq, Yamoto Masaya, Peng Xueni, He Weijing, Cao Yun, Pierro Agostino, Shen Chun, Zhu Haitao
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada.
Pediatr Surg Int. 2025 Jul 18;41(1):218. doi: 10.1007/s00383-025-06043-5.
Human milk-derived exosomes can protect intestinal organoids from lipopolysaccharide induced injury. The aim of this study is to investigate effects of exosomes derived from different periods of lactation on intestinal injury caused by experimental necrotizing enterocolitis (NEC).
Colostrum and mature milk from healthy lactating human mothers were collected and isolated exosomes using serial ultracentrifugation and filtration. NEC was induced in mice pups by hypoxia, gavage of feeding of formula, and lipopolysaccharide (LPS) administration between postnatal days 5 and 9. Breast-fed pups were used as controls. NEC groups received daily gavage feeding of formula with added phosphate-buffered saline (PBS), colostrum exosomes or mature breast milk exosomes. The distal ileum was examined for NEC histology, inflammatory cytokines, and intestinal regeneration abilities.
Compared to NEC group, administration of colostrum and mature milk exosomes in NEC mice resulted in a significant reduction in histological scores of intestinal tissues and decreased expression of inflammatory genes IL-6 and TNF-α. Furthermore, the expression of PCNA, as well as stem cell markers (Lgr5 and Olfm4), increased following exosome treatment, with a corresponding rise in the immunofluorescence staining of Ki67. Compared to mature breast milk exosomes, colostrum exosomes were more effective at enhancing enterocyte proliferation and intestinal regeneration.
Human milk-derived exosome treatment decreases the severity of experimental NEC. Colostrum exosomes induce greater intestinal regeneration compared to mature breast milk exosomes.
人乳来源的外泌体可保护肠类器官免受脂多糖诱导的损伤。本研究旨在探讨不同哺乳期来源的外泌体对实验性坏死性小肠结肠炎（NEC）所致肠道损伤的影响。
收集健康哺乳期母亲的初乳和成熟乳，采用连续超速离心和过滤法分离外泌体。在出生后第5至9天，通过缺氧、灌喂配方奶和给予脂多糖（LPS）诱导幼鼠发生NEC。以母乳喂养的幼鼠作为对照。NEC组每日经口灌喂添加磷酸盐缓冲盐水（PBS）、初乳外泌体或成熟母乳外泌体的配方奶。检查远端回肠的NEC组织学、炎性细胞因子和肠道再生能力。
与NEC组相比，在NEC小鼠中给予初乳和成熟乳外泌体可显著降低肠道组织的组织学评分，并降低炎性基因IL-6和TNF-α的表达。此外，外泌体处理后PCNA以及干细胞标志物（Lgr5和Olfm4）的表达增加，Ki67的免疫荧光染色相应升高。与成熟母乳外泌体相比，初乳外泌体在增强肠上皮细胞增殖和肠道再生方面更有效。
人乳来源的外泌体治疗可降低实验性NEC的严重程度。与成熟母乳外泌体相比，初乳外泌体可诱导更强的肠道再生。
