Microbiome and aging: Trajectories of microbiome age across human ecosystems and their systemic effects

Abstract The “microbiome age,” a computationally derived systemic biosignature, is emerging as a pivotal framework for deciphering host aging trajectories and multi‐organ health status. Beyond merely cataloging taxonomic shifts within specific niches, this concept integrates the cumulative biological effects of microbial community structure, functional homeostasis, ecological interactions, and host regulatory dynamics over time. Accumulating evidence indicates that a deviation between chronological and microbiome age‐termed the “microbiome age gap”‐closely correlates with systemic declines in immunomodulation, metabolic robustness, barrier integrity, and neuroendocrine regulation, positioning it as a potent predictor of healthspan and disease risk. A defining feature of microbial aging is the convergence of divergent ecological niches toward a state of dysbiosis. Despite distinct compositional profiles across the gut, oral cavity, skin, and urogenital tract, these ecosystems commonly exhibit diminished stability, functional remodeling, and altered host–microbe interaction modes with advancing age. Concurrently, site‐specific signatures persist, linking microbial shifts to distinct physiological dimensions such as metabolic‐inflammatory axes, barrier function, and local hormonal environments. In this review, we systematically delineate the theoretical underpinnings and computational strategies for modeling microbiome age. We synthesize current evidence regarding age‐related microbial trajectories across diverse body habitats and propose an integrative framework: microbiome age serves dually as a holistic indicator of systemic aging and a sensitive window into localized organ vulnerability. This perspective not only advances our understanding of host‐microbe interactions in aging but also opens new avenues for precision stratification, personalized intervention, and healthspan management.