AbstractRecent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to varying environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable cofounding effects, and recapitulate age-dependent taxonomic and functional changes in the healthy primate gut microbiota. Herein we performed 16S rRNA gene sequencing, characterized age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed lifelong dynamic changes of primate gut microbiota in the model. While the most significantly age-associated gut microbial taxa were mainly found in commensals such asFaecalibacterium, a set of suspicious pathogens such asHelicobacterwere exclusively enriched in infants, pointing to their potential role in host development. Importantly, topology analysis indicated that the connectivity of gut microbial network was even more age-dependent than taxonomic diversity, with its tremendous decline probably linked to the host’s healthy aging. NetShift analysis identifiedPrevotella 9, Rikenellaceae RC9 gut groupandMegasphaeraas key drivers during gut microbiota maturation and development, actively involved in age-dependent changes in phenotypes and functions of the gut microbial community. The current study demonstrates lifelong age-dependent changes in healthy primate gut microbiota. Our findings indicate potential importance of appropriate exposure to suspicious pathogens in infant development. The age-associated baseline profiles and driver microbes of primate gut microbiota in the current study could provide new insight into its role in the host’s development and healthy aging.