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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| Format: | Article |
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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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| author | Hung-Chih Chen Yu-Che Cheng Marvin L. Hsieh Po-Ju Lin Emily F. Wissel Theodore Steward Cindy M. C. Chang Jennifer Coonen Timothy A. Hacker Timothy J. Kamp Patrick C. H. Hsieh |
| author_facet | Hung-Chih Chen Yu-Che Cheng Marvin L. Hsieh Po-Ju Lin Emily F. Wissel Theodore Steward Cindy M. C. Chang Jennifer Coonen Timothy A. Hacker Timothy J. Kamp Patrick C. H. Hsieh |
| author_sort | Hung-Chih Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-41b0abb9c232427da33f7170127e0a26 |
| institution | Kabale University |
| issn | 2057-3995 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj-art-41b0abb9c232427da33f7170127e0a262025-01-19T12:13:08ZengNature Portfolionpj Regenerative Medicine2057-39952025-01-0110111110.1038/s41536-025-00390-6Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion modelHung-Chih Chen0Yu-Che Cheng1Marvin L. Hsieh2Po-Ju Lin3Emily F. Wissel4Theodore Steward5Cindy M. C. Chang6Jennifer Coonen7Timothy A. Hacker8Timothy J. Kamp9Patrick C. H. Hsieh10Institute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaModel Organisms Research Core, Department of Medicine, University of Wisconsin-MadisonInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaModel Organisms Research Core, Department of Medicine, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin-MadisonModel Organisms Research Core, Department of Medicine, University of Wisconsin-MadisonDepartment of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-MadisonInstitute of Biomedical Sciences, Academia SinicaAbstract 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.https://doi.org/10.1038/s41536-025-00390-6 |
| spellingShingle | Hung-Chih Chen Yu-Che Cheng Marvin L. Hsieh Po-Ju Lin Emily F. Wissel Theodore Steward Cindy M. C. Chang Jennifer Coonen Timothy A. Hacker Timothy J. Kamp Patrick C. H. Hsieh Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model npj Regenerative Medicine |
| title | Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model |
| title_full | Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model |
| title_fullStr | Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model |
| title_full_unstemmed | Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model |
| title_short | Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model |
| title_sort | gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia reperfusion model |
| url | https://doi.org/10.1038/s41536-025-00390-6 |
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