Gut microbiome and aging-related disorders: mechanistic insights and emerging microbiome-targeted therapies for healthy aging

Background The human gut harbors a diverse and dense microbial community that maintains metabolic, immune, and intestinal homeostasis through a symbiotic relationship with the host. Aging is a complex biological process that involves alterations in the gut microbiome, including decreased microbial diversity and a decline in beneficial microbiota that produce useful metabolites, which impair intestinal barrier function and enhance chronic low-grade inflammation (inflammaging). Scope This review explores current evidence on the interaction between aging and the gut microbiome, emphasizing its impact on age-associated diseases, such as frailty and sarcopenia, cardiovascular issues, type 2 diabetes, obesity, osteoporosis, and neurodegenerative conditions. It further delves into the distinct microbial profiles of centenarians and evaluates microbiome-targeted interventions, such as dietary approaches, probiotics, prebiotics, synbiotics, fecal microbiota transplants, caloric restriction, intermittent fasting, and pharmaceutical agents, by synthesizing evidence from both human and animal research to emphasize their potential in fostering healthy aging and increased longevity. Key findings Evidence from human and preclinical studies suggests that alterations in the gut microbiome associated with aging facilitate immune dysregulation, metabolic dysfunction, and the progression of various chronic diseases. Whereas, centenarians possess distinctive microbial signatures rich in beneficial metabolites that could promote healthy aging and prolonged life. Additionally, microbiome-targeted interventions have demonstrated promise in enhancing gut microbial diversity and host wellbeing, though their clinical effectiveness needs additional validation. Conclusion The gut microbiome is a potential focus for supporting healthy aging and warding off age-related illnesses. Nonetheless, its significant inter-individual variability emphasizes the necessity for personalized microbiome-based approaches, which require validation through extensive longitudinal studies and properly structured randomized controlled trials to demonstrate causality and verify long-term effectiveness.