Dynamic change patterns of the human gut microbiota-fluctuation, loss-acquisition, and turnover-and their underlying causes

The temporal dynamics of the gut microbiome are critical to human health, yet their patterns and underlying drivers remain poorly characterized at a monthly resolution and strain level. This knowledge gap limits the development of targeted microbiome interventions. Here, we integrate longitudinal analyses across three human cohorts-a cross-sectional cohort (<i>n</i> = 190), an intensive 52-month time series (<i>n</i> = 7), and a paired 6-month cohort (<i>n</i> = 43)-together with a humanized mouse model under antibiotic perturbation. Using shotgun metagenomics (516 samples), we resolve microbial dynamics at species and strain resolution. We identify three distinct modes of temporal variation: relative abundance fluctuations, species loss-acquisition events, and strain turnover. Strain turnover contributes substantially to the dynamic reservoir of functional genes, including those associated with virulence and antibiotic resistance. These dynamics are influenced by antibiotic exposure and microbial interspecies interactions. Our work provides a month-scale atlas of gut microbiome variation, revealing widespread transient colonization and strain-level plasticity, thereby offering a refined framework for understanding microbiome stability and personalized microbial ecology.