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牛奶蛋白过敏中肠道屏障受损与肠道菌群及其代谢产物变化相关。

Impairment of intestinal barrier associated with the alternation of intestinal flora and its metabolites in cow's milk protein allergy.

作者信息

Yu Zhidan, Yue Lingling, Yang Zhaojie, Wang Yuesheng, Wang Zihui, Zhou Fang, Li Chan, Li Lifeng, Zhang Wancun, Li Xiaoqin

机构信息

Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Zhengzhou Key Laboratory of Children's Digestive Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.

Henan Province Orthopedic Hospital, Zhengzhou, 450000, China.

出版信息

Microb Pathog. 2023 Oct;183:106329. doi: 10.1016/j.micpath.2023.106329. Epub 2023 Aug 31.

DOI:10.1016/j.micpath.2023.106329
PMID:37659726
Abstract

Cow's milk protein allergy (CMPA), one of the most prevalent food allergies, seriously affects the growth and development of infants and children with the rising incidence and prevalence. The dysbiosis of intestinal flora acts to promote disease including allergic disease. Therefore, studying the role of intestinal flora in allergic diseases holds great promise for developing effective strategies to mitigate the risk of food allergies. This study aims to elucidate the role of disrupted intestinal flora and its metabolites in children with CMPA.16S rDNA sequence analysis was applied to characterize the changes in the composition of intestinal flora. The findings revealed heightened diversity of intestinal flora in CMPA, marked by decreased abundance of Firmicutes and Bacteroidetes, and increased abundance of Proteobacteria and Actinobacteria. Furthermore, metabolite analysis identified a total of 1245 differential metabolites in children with CMPA compared to those in healthy children. Among these, 765 metabolites were down-regulated, while 480 were up-regulated. Notably, there were 10 negative differential metabolites identified as bile acids and derivatives, including second bile acids, such as deoxycholic acid, ursodeoxycholic acid and isoursodexycholic acid. The intestinal barrier was further analyzed and showed that the enterocytes proliferation and the expression of Claudin-1, Claudin-3 and MUC2 were down-regulated with the invasion of biofilm community members in the CMPA group. In summary, these findings provide compelling evidence that food allergies disrupt intestinal flora and its metabolites, consequently damaging the intestinal barrier's integrity to increase intestinal permeability and immune response.

摘要

牛奶蛋白过敏(CMPA)是最常见的食物过敏之一,随着发病率和患病率的上升,严重影响婴幼儿的生长发育。肠道菌群失调会促进包括过敏性疾病在内的疾病发展。因此,研究肠道菌群在过敏性疾病中的作用对于制定有效的策略以降低食物过敏风险具有很大的前景。本研究旨在阐明肠道菌群紊乱及其代谢产物在CMPA儿童中的作用。应用16S rDNA序列分析来表征肠道菌群组成的变化。研究结果显示,CMPA患儿肠道菌群多样性增加,其特征为厚壁菌门和拟杆菌门丰度降低,变形菌门和放线菌门丰度增加。此外,代谢产物分析发现,与健康儿童相比,CMPA患儿共有1245种差异代谢产物。其中,765种代谢产物下调,480种上调。值得注意的是,有10种负差异代谢产物被鉴定为胆汁酸及其衍生物,包括次级胆汁酸,如脱氧胆酸、熊去氧胆酸和异熊去氧胆酸。进一步分析肠道屏障发现,在CMPA组中,随着生物膜群落成员的侵入,肠细胞增殖以及Claudin-1、Claudin-3和MUC2的表达下调。总之,这些发现提供了令人信服的证据,即食物过敏会破坏肠道菌群及其代谢产物,从而损害肠道屏障的完整性,增加肠道通透性和免疫反应。

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