Abstract The significance of the urinary microbiome in maintaining health and contributing to disease development is increasingly recognized. However, a comprehensive understanding of this microbiome and its influencing factors remains elusive. Utilizing whole metagenomic and whole-genome sequencing, along with detailed metadata, we characterized the urinary microbiome and its influencing factors in a cohort of 1579 Chinese individuals. Our findings unveil the distinctiveness of the urinary microbiome from other body sites, delineating five unique urotypes. We identified 137 host factors significantly influencing the urinary microbiome, collectively explaining 13.16% of the variance in microbial composition. Notably, gender-related factors, including sex hormones, emerged as key determinants in defining urotype groups and microbial composition, with the urinary microbiome exhibiting strong predictive ability for gender (AUC=0.815). Furthermore, we discovered 43 genome-wide significant associations between host genetic loci and specific urinary bacteria, particularly Acinetobacter , linked to 8 host loci ( p &lt; 5x10 −8 ). These associations were also modulated by gender and sex hormone levels. In summary, our study provides novel insights into the impact of host genetics and other factors on the urinary microbiome, shedding light on its implications for host health and disease.

Unraveling the impact of host genetics and factors on the urinary microbiome in a young population