Age-related Gut Microbiome Profile and Reversal of Microbial Imbalance by Trimetazidine Intervention

Background Despite the recognized link between microbiome and aging, the dynamic characteristics of the gut microbiota community across the human lifespan and their mechanistic contributions to aging remain unclear. Purpose In this study, we employed metagenomic sequencing and 16S rRNA sequencing to delineate the dynamic characteristics of gut microbiota during aging in human and rat cohorts, as well as exploring the potential mechanisms on microbiome-regulated aging in rats. Results Multi-cohort gut microbiome results revealed that microbial alterations during aging follow a nonlinear trajectory. Functional enrichment analysis showed that lipid metabolism was increased with age in both human and animal models, consistent with marked abundance changes in gut microbiota implicated in lipid metabolism (e.g., Catenulispora and Luteipulveratus ). Subsequently, Trimetazidine, a fatty acid oxidation inhibitor, significantly suppressed the abundance of lipid metabolism associated-gut microbiota in aging rats. Further functional profiling and experimental validation confirmed that trimetazidine inhibited fatty acid oxidation, as well as inhibited expression of senescence markers p21 and p16. Conclusions In conclusion, gut microbiota composition undergoes age-dependent remodeling in humans and rats, with significant enrichment of fatty acid oxidation-related microbiome in aged states. Trimetazidine contributes to alleviating aging process by modulating gut microbial homeostasis and fatty acid metabolism.