Microbiome remodeling during aging: Integrative multi-omics and spatiotemporal perspectives on immune and metabolic regulation.

Changes in the gut microbiota occur throughout the human lifespan, and maintaining microbial homeostasis plays a critical role in promoting healthy aging. In recent years, substantial progress has been made in elucidating the mechanistic links between aging and microbiota remodeling, highlighting the central role of microbiota-host interactions in regulating immune responses and maintaining metabolic homeostasis. These findings provide new potential targets for the precision prevention and treatment of age-related diseases. This review systematically summarizes the patterns of gut microbiota succession across different stages of the human life cycle, including infancy, adolescence, adulthood, and old age, as well as the mechanisms through which the microbiota regulates immune and metabolic functions. Furthermore, the role of the gut microbiota as a key mediator linking aging with an increased risk of chronic inflammation, cardiovascular disease, cognitive impairment, neurodegenerative disorders, and cancer was explored. In addition, this review evaluates the therapeutic potential of microbiota-targeted interventions, such as dietary modification, probiotic and prebiotic supplementation, fecal microbiota transplantation (FMT), and lifestyle interventions-in maintaining microbiome homeostasis and mitigating age-related diseases. The feasibility of personalized microbiota-based intervention strategies is also discussed. Finally, we highlight the current challenges and limitations in this field and outline future research directions. In particular, integrating multi-omics approaches with metagenomic sequencing, including emerging spatial and spatiotemporal multi-omics technologies, is crucial for advancing our understanding of the complex interactions within the gut microbiome. These insights provide a theoretical framework for optimizing anti-aging therapeutic strategies and promoting healthy lifespan extension.