Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model
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 im...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-025-00390-6 |
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| Summary: | 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. |
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| ISSN: | 2057-3995 |