Poster T13 - Gut Microbiota Modulation by Immunosuppression and Cardiac Cell Therapy in a Nonhuman Primate Ischemia/Reperfusion Model of Cardiac Regeneration
Distinguished Research Fellow Institute of Biomedical Sciences, Academia Sinica Taipei, United States
Introduction: End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Gut microbial dysbiosis influences disease progression and treatment outcomes. While well-studied in hematopoietic cell and solid organ transplantation, the role of gut microbiota in cardiac cell therapy and immunosuppression remains unexplored.
Materials and
Methods: Nonhuman primates (NHP) were subjected to cardiac ischemia/reperfusion (IR) injury. The NHP IR model were treated with either human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) or combination of CM and hiPSC-derived endothelial cells (EC) in the presence of immunosuppression. Stool and plasma samples were collected for 16S rRNA V3-V4 sequencing and Liquid Chromatography Mass Spectrometry (LC-MS) metabolomics, respectively.
Results, Conclusions, and Discussions: We investigated gut microbiota dynamics in response to immunosuppression and cell therapy in the NHP cardiac IR model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of hiPSC-derived EC and CM also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.
