Associations between gut microbiome and 24-hour blood pressure variability: a cross-sectional study highlighting sex...

Blood pressure (BP) variability is an independent risk factor for cardiovascular disease. Gut microbiome (GM) regulates BP, but its association with BP variability remains unclear. We examined the association of GM, determined by stool shotgun metagenomic sequencing, with 24-hour BP average real variability (ARV) assessed by ambulatory BP monitoring in 235 community-dwelling adults from Hong Kong (111 men and 124 women, mean age 54 ± 6 years) using covariate-adjusted statistical models. The GM alpha diversity was negatively associated with systolic BP (SBP) ARV in the full cohort, driven by women. In men, beta diversity of both GM species and function was associated with SBP ARV, while Bacteroides nordii and the steroid hormone biosynthesis pathway had a positive association with SBP ARV. Bacteroides nordii emerged as the key species driving the significant positive association of steroid hormone biosynthesis and other pro-pathogenic pathways with SBP ARV, including lipopolysaccharide biosynthesis, phenylalanine, and sulfur metabolism in men, warranting further investigation for its causal role. We demonstrated distinct signatures of GM dysbiosis, composition, and function with minimal overlap between men and women with increased 24-hour SBP variability. Our work suggests that sex differences should be an important consideration in mechanistic and therapeutic investigations of GM-mediated BP variability.