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

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 1,579 Chinese individuals. Our findings unveil the distinctiveness of the urinary microbiome from other four body sites, delineating five unique urotypes dominated by sp. PDC80, and , respectively. We identified 108 host factors significantly influencing the urinary microbiome, collectively explaining 12.92% of the variance in microbial composition. Notably, gender-related factors, including sex hormones, emerged as key determinants in defining urotype groups, microbial composition and pathways, with the urinary microbiome exhibiting strong predictive ability for gender (area under the curve [AUC] = 0.843). Furthermore, we discovered 43 genome-wide significant associations between host genetic loci and specific urinary bacteria, in particular, linked to eight host loci ( < 5 × 10 ). 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. The urinary microbiome, essential to human health, reveals its unique qualities in our study of 1,579 Chinese individuals. We identified distinctive microbial profiles, or "urotypes," and uncovered strong gender-related influences, particularly from sex hormones, on these microbial communities. Our research highlights significant genetic associations affecting specific urinary bacteria, indicating a deep interaction between our genetics and our microbiome. These insights not only enhance our understanding of the urinary microbiome's role in health and disease but also open new pathways for personalized medical strategies, making our findings crucial for future diagnostic and therapeutic innovations. This work underscores the intricate relationship between our body's biological processes and the microorganisms within, providing valuable knowledge for both scientific and medical communities.