Longitudinal gut microbiota tracking reveals the dynamics of horizontal gene transfer
Haoran Peng, Sergio Andreu‐Sánchez, Angel J. Ruiz‐Moreno, Asier Fernández-Pato, Jiafei Wu, Ranko Gaćeša, Alexandra Zhernakova, Daoming Wang, Jingyuan Fu
Abstract
Horizontal gene transfer (HGT) is a major driver of bacterial evolution, but its role in shaping the human gut microbiome over time remains poorly understood. Here, we present a longitudinal metagenomic analysis of 676 fecal samples from 338 individuals in the Lifelines-DEEP study collected ~4 years apart, using a newly developed workflow to detect recent HGT events from metagenome-assembled genomes. We identified 5,644 high-confidence HGT events occurring within the past ~10,000 years across 116 gut bacterial species. We find that species pairs with an HGT relationship were significantly more likely to maintain stable co-abundance relationships over the 4-year period, suggesting that gene exchange contributes to community stability. Notably, HGT and strain replacement act together to disseminate mobile genes in the population. Furthermore, our observation that an individual’s mobile gene pool remains highly personalized and stable over time indicates that host lifestyles drive specific gene transfer. For example, proton pump inhibitor usage is linked to increased transfer of multidrug transporter genes. Our findings demonstrate, at the individual gut microbiome level, that HGT is both an integral and stabilizing force in the human gut ecosystem and an important mechanism for disseminating adaptive functions, underscoring HGT potential for tracking host lifestyle. Here, via longitudinal metagenomic analysis of 676 fecal samples from 338 individuals in the Lifelines-DEEP study, the authors identify ongoing gene-sharing among human gut bacteria that supports community stability and spreads helpful functions. These gene-sharing signatures are highly personal, illuminating how host lifestyle shapes gut microbes over time.