A global metagenomic atlas of aging identifies a microbiota phase transition associated with disease risk

Biological aging has been associated with altered risk of aging-related diseases, but the contribution of the gut microbiota to this process remains poorly understood. Here, we constructed an interpretable gut microbiota age clock using metagenomic data from 8115 fecal samples across five continents. We discovered a key microbial perturbation occurring at 56-60 years of chronological age, which was validated in an independent cohort of 2263 metagenomes. This perturbation was associated with a decline in ecological stability and substantial changes in the abundance of core species. Notably, the association between gut microbiota age and diseases was identified to be significantly altered before and after this inflection time. Moreover, within-species analyses uncovered phylogenetic divergence for seven age-related species, such as Escherichia coli, alongside functional alterations in older individuals, including enhanced cell motility, carbohydrate metabolism and horizontal gene transfer. Overall, our global gut microbiome atlas uncovers a critical age transition phase, highlighting opportunities for microbiota-based therapies and offering novel insights into evolutionary dynamics during aging.