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

Chen, Hung-Chih; Cheng, Yu-Che; Hsieh, Marvin L; Lin, Po-Ju; Wissel, Emily F; Steward, Theodore; Chang, Cindy M C; Coonen, Jennifer et al. · NPJ Regen Med · 2025

basic_science · Level V

Where this comes from

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.