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

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

doi:10.1038/s41536-025-00390-6

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

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

Authors

Hung-Chih Chen¹, Yu-Che Cheng², Marvin L Hsieh³, Po-Ju Lin², Emily F Wissel², Theodore Steward^{2

4}, Cindy M C Chang³, Jennifer Coonen⁵, Timothy A Hacker³, Timothy J Kamp⁶, Patrick C H Hsieh^{7

8

9}

Affiliations

¹ Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan. byron.hc.chen@gmail.com.
² Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
³ Model Organisms Research Core, Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA.
⁴ Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
⁵ Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
⁶ Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.
⁷ Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan. phsieh@ibms.sinica.edu.tw.
⁸ Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI, 53705, USA. phsieh@ibms.sinica.edu.tw.
⁹ Institute of Medical Genomics and Proteomics and Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, 106, Taiwan. phsieh@ibms.sinica.edu.tw.

PMID: 39809790
DOI: 10.1038/s41536-025-00390-6

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.

Grants and funding

NHRI -EX112-11203SI/National Health Research Institutes (NHRI)