Abstract
Age-related changes in the microbiome have been reported in previous studies; however, direct evidence for their association with frailty is lacking. Here, we introduce biological age based on gut microbiota (gAge), an integrated prediction model that integrates gut microbiota data from different perspectives with potential background factors for aging assessment. Simulation results show that, compared with a single model, the ensemble model can not only significantly improve the prediction accuracy, but also make full use of the data in unpaired samples. From this, we identified markers associated with age development and grouped markers into accelerated aging and mitigated aging according to their effect on the prediction. Importantly, the application of gAge to an elderly cohort with different frailty levels confirmed that gAge and its predictive residuals are closely related to the individual's health status and frailty stage, and age-related markers overlap significantly with disease and frailty characteristics. Furthermore, we applied the gAge prediction model to another independent cohort of the elderly population for aging assessment and found that gAge could effectively represent the aging population. Overall, our study explains the association between the gut microbiota and frailty, providing potential targets for the development of gut microbiota-based targeted intervention strategies for aging.