Age-Related Alterations in Human Gut Microbiota and Intestinal Aging: Microbial Signatures, Disease Associations and Intervention Strategies

Aging is accompanied by progressive alterations in gut homeostasis, characterized by gut microbiota dysbiosis, impaired intestinal barrier function, immune dysregulation, and chronic low-grade inflammation. Increasing evidence indicates that age-related gut microbial remodeling is closely associated with the development of multiple age-associated disorders, including frailty, sarcopenia, cardiovascular diseases, and neurodegenerative diseases. However, existing reviews have primarily focused on individual aspects of gut microbiota-mediated aging, whereas a systematic framework integrating gut microbial dysbiosis, intestinal aging, and the development of multiple age-related diseases through shared pathogenic mechanisms remains lacking. This review provides a comprehensive synthesis of age-related alterations in human gut microbiota, with particular emphasis on bacterial taxa consistently associated with healthy aging and age-related diseases. We further integrate current evidence to examine the associations between age-related microbial alterations and intestinal aging, with particular attention to microbial function, barrier integrity, and host immune responses. Finally, we review microbiota-targeted interventions, including fecal microbiota transplantation, probiotics, prebiotics, and dietary modulation, and discuss their potential and limitations in promoting healthy aging. By integrating mechanistic evidence with findings from human observational cohorts and clinical intervention studies, this review provides a translational framework for understanding microbiota-mediated intestinal aging and highlights future directions for precision microbiota-based strategies to promote healthy aging.