Sex-associated association between gut Faecalibacterium prausnitzii and hypertension in males

Jing Fu¹Guosen Bu²Salamaiti Aimaier³Yuchun Yang¹Zhen Bao¹Muhuyati Wulasihan^1*

• ¹Department of General Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
• ²Department of Neurology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
• ³Department of Heart Failure, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

While gut microbiota dysbiosis has been implicated in hypertension, the sex-associated microbial signatures and their underlying mechanisms remain poorly understood, especially in populations inhabiting unique geographical and climatic conditions. Through an integrated approach combining 16S rRNA sequencing, shotgun metagenomics, and serum metabolomics, we systematically investigated the sex-associated characteristics of gut microbiota in hypertension a Xinjiang cohort of 200 participants. Initial cohort analysis identified Faecalibacterium as a male-associated biomarker for hypertension. Subsequent species-level characterization demonstrated that Faecalibacterium prausnitzii (F. prausnitzii) showed significant negative correlations with systolic blood pressure. This male-associated association was consistently observed across both 16S rRNA sequencing and shotgun metagenomic datasets. Then, our integrated analysis suggests a potential pathway whereby F. prausnitzii may be linked to systolic blood pressure in males, with N-phenylacetylglutamine (PAGln) identified as a potential mediating metabolite. Our study establishes the microbial-metabolite-clinical trait axis in sex-associated hypertension pathophysiology. Our study significantly advances our understanding of sex-driven host-microbe interactions.