Different ages of gut microbiota diversity and metabolic pattern in rhesus macaques.

INTRODUCTION: The gut microbiota and its metabolites change dynamically with age, but their trajectories and links to healthy aging are unclear, hindering the development of related interventions. METHODS: We utilized captive rhesus macaques across three age groups, conducting 16S sequencing and targeted metabolomics analysis of fecal matter. RESULTS: Lactobacillus predominated in young monkeys. Old adult monkeys exhibited the most severe intestinal inflammation, matching the dominance of Proteobacteria, Prevotella, and Fusobacterium. In oldest monkeys, the gut microbiota tended to be dominated by the short-chain fatty acid-producing Butyricicoccus and Christensenellaceae. Twenty-one metabolites gradually decrease with age, including omega-3 fatty acids, aspartic acid, ornithine, and TCA cycle-related metabolites. The urea cycle, glycine/serine metabolism, and arginine/proline metabolism undergo age-related changes, likely reflecting altered intestinal microbial metabolic activity and potentially affecting hepatic ammonia metabolism. DISCUSSION: Ornithine or a-ketoglutarate supplementation mitigates cellular senescence in liver cells and bone marrow mesenchymal stem cells. Our findings elucidate the dynamic changes of gut microbiota and metabolites with age, providing critical support for the use of rhesus monkeys as an animal model to study the role of gut microbiota in human aging.