炎症性肠病中间充质干细胞对肠道微生物群和微生物群相关功能的影响:动物模型临床前证据的系统综述。

Airu Liu, Chenyang Li, Chen Wang, Xiaonan Liang, Xiaolan Zhang
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引用次数: 0

摘要

背景:炎症性肠病(IBD)是一个全球性的健康问题,肠道微生物群失调在其中起着关键的致病作用。间充质干细胞以其强大的免疫调节和组织修复能力显示出良好的应用前景。最近的实验数据表明,间充质干细胞还调节肠道微生物群的组成。本综述首次分析了IBD模型中MSCs和肠道微生物群调节之间的研究数据,旨在评估肠道微生物群在MSCs修复IBD中的作用。方法:截至2023年1月,在PubMed、Web of Science和Scopus数据库上进行了全面、结构化的文献检索。偏差评估的质量和风险遵循PRISMA指南和SYRCLE的工具。结果:共纳入9项关于动物模型的临床前研究。尽管MSCs的应用剂量和途径非常不同,但结果表明MSCs对肠道炎症表现出保护作用,包括小鼠的一般评估、免疫调节和肠道屏障完整性。同时,研究表明,MSC给药对肠道菌群组成有积极影响,其特征是恢复厚壁菌门/拟杆菌门的平衡和减少变形菌。有益细菌阿克曼菌、双歧杆菌和乳酸杆菌也明显富集,致病菌志贺氏杆菌则相反减少。α和β多样性也被调节为与健康小鼠相似。微生物代谢功能,如次级胆汁酸的生物合成和鞘脂代谢,以及一些与细胞再生有关的生物行为也上调,而癌症功能和特征较差的细胞功能下调。结论:目前的数据支持MSC给药对肠道微生物群的重塑作用,这为MSC治疗IBD提供了潜在的治疗机制。有必要在人类和动物模型中进行更多的研究,以进一步证实肠道菌群在MSCs修复IBD中的作用。
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Impact of Mesenchymal Stem Cells on the Gut Microbiota and Microbiota Associated Functions in Inflammatory Bowel Disease: A Systematic Review of Preclinical Evidence on Animal Models.

Background: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has shown promising application prospects for its powerful immune regulation and tissue repair ability. Recent experimental data suggest that MSCs also regulate the composition of gut microbiota. The current review analyzed, for the first time, the research data linking MSCs and gut microbiota modulation in IBD models aiming at assessing the role of gut microbiota in MSCs repair of IBD.

Methods: A comprehensive and structured literature search was performed up to January 2023 on the PubMed, Web of Science, and Scopus databases. The quality and risk of bias assessment followed the PRISMA guidelines and SYRCLE's tool.

Results: A total of nine pre-clinical studies on animal models were included. Although the dose and route of MSCs applied were quite heterogeneous, results showed that MSCs displayed protective effects on intestinal inflammation, including mice general assessment, immunoregulation, and intestinal barrier integrity. Meanwhile, studies showed positive effects on the composition of gut flora with MSCs administration, which had been characterized by restoration of Firmicutes/ Bacteroides balance and reduction of Proteobacteria. The beneficial bacteria Akkermansia, Bifidobacterium, and Lactobacillus were also distinctly enriched, and the pathogenic bacteria Escherichia-Shigella was conversely decreased. The alpha and beta diversity were also regulated to resemble those of healthy mice. Microbial metabolic functions, such as biosynthesis of secondary bile acid and sphingolipid metabolism, and some biological behaviors related to cell regeneration were also up-regulated, while cancer function and poorly characterized cellular function were down-regulated.

Conclusion: Current data support the remodeling effect on gut microbiota with MSC administration, which provides a potential therapeutic mechanism for MSCs in the treatment of IBD. Additional studies in humans and animal models are warranted to further confirm the role of gut microflora in MSCs repairing IBD.

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