Abstract

The human microbiome, composed of trillions of bacteria, archaea, fungi, and viruses, is essential for maintaining 
metabolic, immune, and neurological homeostasis. With aging, the composition and function of microbial 
communities undergo profound changes, contributing to systemic inflammation, immune dysfunction, metabolic 
derangements, and neurodegeneration. Hallmarks of aging, including genomic instability, cellular senescence, and 
mitochondrial dysfunction, intersect with age-associated dysbiosis, exacerbating the onset and progression of 
chronic conditions such as cardiovascular disease, diabetes, and Alzheimer’s disease. Altered microbiota 
composition reduces resilience, impairs immune regulation, and disrupts gut–brain communication, fostering 
frailty and cognitive decline. Conversely, microbiome-targeted strategies, including probiotics, prebiotics, dietary 
interventions, and fecal microbiota transplantation (FMT), demonstrate potential for restoring balance and 
promoting healthy aging. Advances in multi-omics and machine learning are improving mechanistic 
understanding and enabling personalized interventions, though challenges remain in standardization, 
reproducibility, and long-term efficacy. This review summarizes current insights into the bidirectional relationship 
between microbiome dynamics and aging, highlighting therapeutic opportunities and future research directions. 
Keywords: Microbiome, Aging, Immunosenescence, Gut–brain axis, and Fecal microbiota transplantation.