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在非人类灵长类动物缺血/再灌注模型中，通过免疫抑制进行心脏细胞治疗时对肠道微生物群的调节

Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model.

作者信息

Chen Hung-Chih, Cheng Yu-Che, Hsieh Marvin L, Lin Po-Ju, Wissel Emily F, Steward Theodore, Chang Cindy M C, Coonen Jennifer, Hacker Timothy A, Kamp Timothy J, Hsieh Patrick C H

机构信息

Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.

Model Organisms Research Core, Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA.

出版信息

NPJ Regen Med. 2025 Jan 15;10(1):2. doi: 10.1038/s41536-025-00390-6.

DOI:10.1038/s41536-025-00390-6
PMID:39809790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11733301/
Abstract

Gut microbiota affect transplantation outcomes; however, the influence of immunosuppression and cell therapy on the gut microbiota in cardiovascular care remains unexplored. We investigated gut microbiota dynamics in a nonhuman primate (NHP) cardiac ischemia/reperfusion model while under immunosuppression and receiving cell therapy with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (EC) and cardiomyocytes (CM). Both immunosuppression and EC/CM co-treatment increased gut microbiota alpha diversity. Immunosuppression promoted anaerobes, such as Faecalibacterium, Streptococcus, Anaerovibrio and Dialister, and altered amino acid metabolism and nucleosides/nucleotides biosynthesis in host plasma. EC + CM cotreatment favors Phascolarctobacterium, Fusicatenibacter, Erysipelotrichaceae UCG-006, Veillonella and Mailhella. Remarkably, gut microbiota of the EC/CM co-treatment group resembled that of the pre-injury group, and the NHPs exhibited a metabolic shift towards amino acid and fatty acid/lipid biosynthesis in plasma following cell therapy. The interplay between shift in microbial community and host homeostasis during treatment suggests gut microbiome modulation could improve cell therapy outcomes.

摘要

肠道微生物群会影响移植结果；然而，免疫抑制和细胞疗法对心血管护理中肠道微生物群的影响仍未得到探索。我们在非人类灵长类动物（NHP）心脏缺血/再灌注模型中，研究了在免疫抑制状态下以及接受人诱导多能干细胞（hiPSC）衍生的内皮细胞（EC）和心肌细胞（CM）进行细胞治疗时的肠道微生物群动态变化。免疫抑制和EC/CM联合治疗均增加了肠道微生物群的α多样性。免疫抑制促进了诸如粪杆菌属、链球菌属、厌氧弧菌属和戴阿李斯特菌属等厌氧菌的生长，并改变了宿主血浆中的氨基酸代谢以及核苷/核苷酸生物合成。EC+CM联合治疗有利于考拉杆菌属、梭菌属、丹毒丝菌科UCG-006、韦荣球菌属和Mailhella菌属的生长。值得注意的是，EC/CM联合治疗组的肠道微生物群与损伤前组相似，并且在细胞治疗后，NHP的血浆表现出向氨基酸和脂肪酸/脂质生物合成的代谢转变。治疗期间微生物群落变化与宿主内环境稳态之间的相互作用表明，调节肠道微生物群可能会改善细胞治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8c/11733301/063f01e04cdd/41536_2025_390_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8c/11733301/063f01e04cdd/41536_2025_390_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8c/11733301/3487571b58df/41536_2025_390_Fig1_HTML.jpg
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