Gut Microbiota and Ageing: Mechanisms, Age-Related Diseases, and Therapeutic Perspectives.

Population ageing has intensified interest in biological mechanisms that influence healthspan and susceptibility to age-related diseases. Among these mechanisms, the gut microbiota has emerged as an important modulator of immune, metabolic, and neurophysiological processes involved in ageing. This narrative review critically synthesises current evidence regarding age-related alterations in gut microbiota composition and function, their relationship with inflammaging and the hallmarks of ageing, and the potential role of microbiota-targeted interventions in promoting healthy ageing. A comprehensive narrative literature search was conducted using PubMed, Scopus, and Web of Science, focusing primarily on human observational studies, longitudinal cohorts, mechanistic investigations, and interventional trials published in peer-reviewed journals between 2010 and 2025. Priority was given to studies examining older adults, frailty, longevity, and microbiota-mediated mechanisms relevant to ageing biology. Current evidence suggests that ageing is frequently associated with reduced microbial diversity, depletion of beneficial short-chain fatty acid-producing taxa, altered intestinal barrier integrity, and increased abundance of pro-inflammatory microorganisms. These alterations are linked to inflammaging and may contribute to neurodegenerative, cardiovascular, metabolic, musculoskeletal, and joint diseases, including osteoporosis, sarcopenia, rheumatoid arthritis, and osteoarthritis. However, causality remains incompletely established in humans, and substantial inter-individual variability exists. Studies of centenarians suggest that preservation of specific microbial metabolic functions may be associated with healthier ageing trajectories. Dietary interventions, particularly Mediterranean-style diets rich in fibre and polyphenols, alongside exercise, prebiotics, probiotics, and emerging microbiota-targeted therapies, show potential to modulate these pathways. Despite significant advances, major challenges remain regarding causality, reproducibility, standardisation of microbiome analyses, and personalised therapeutic implementation. Future longitudinal multi-omics studies and precision microbiome interventions will be essential to clarify the translational role of the gut microbiota in healthy ageing and age-related disease prevention.