Abstract
The gut microbiome has emerged as a critical regulator of human aging and healthspan, with age-related dysbiosis increasingly implicated in a broad spectrum of aging-associated diseases. This review synthesizes evidence linking gut microbial alterations to infectious diseases, antimicrobial resistance, autoimmune, neurodegenerative, psychiatric, cancer, metabolic, kidney, cardiovascular, bone, and muscular diseases, highlighting shared mechanisms such as chronic inflammation, immune dysregulation, and metabolite imbalance. We further explore how enabling technologies, including functional multi-omics, synthetic biology, artificial intelligence-driven analytics, biobanking, and autologous fecal microbiota transplantation, are revolutionizing microbiome research and the design of interventions. Ethical considerations surrounding microbiome-based therapies are also addressed. To translate these scientific insights into clinical innovations, we formulate the PRIME framework: a five-phase roadmap encompassing Profiling, Reviewing, Identifying, Mapping, and Evaluating microbiome-based interventions. By integrating microbiome science, aging biology, and emerging technologies, this review provides a comprehensive blueprint for advancing precision medicine and promoting healthy aging. Furthermore, it emphasizes the importance of building future-ready capabilities to navigate the evolving landscape of age-related diseases and microbiome-driven therapeutic innovations.