Background: Blood pressure (BP) variability is an independent risk factor for cardiovascular disease (CVD). BP variability has been associated with cardiovascular organ damage and is a potential therapeutic target for the prevention of CVD. Recently, the gut microbiome (GM) has been shown to have a pathological role in hypertension, however, the association between GM and BP variability is poorly understood. Methods: 241 community-dwelling individuals free of symptomatic CVD from Hong Kong (113 males and 128 females, mean age 54±6 years) underwent ambulatory BP monitoring and stool microbiota shotgun sequencing. BP variability was determined as systolic/diastolic BP (SBP/DBP) coefficient of variation (CoV), nighttime dipping, and morning BP surge (MBPS). Sleep latency was estimated using 7-day Actigraphy data. Associations of BP variability with GM, and plasma and stool short-chain fatty acids (SCFAs) were analyzed under statistical models adjusting for age, sex, serum glucose and lipids, sodium intake assessed by urine analysis, menopause status, smoking, fatty liver, BP and sleep latency. Results: Women had a significantly higher 24-hour SBP ( p =0.0005) and DBP ( p =0.002) CoV than men. 24-hour SBP CoV had a negative association with GM α-diversity (Shannon and Simpson’s index: all P <0.05) and a positive association with Firmicutes/Bacteroidetes ratio ( P <0.05), suggesting gut dysbiosis in participants with higher systolic BP variability. Several GM species and SCFAs were significantly associated with the indices of BP variability in both men and women. Notably, Parabacteroides merdae had a negative association with both systolic and diastolic BP CoV (all P <0.05-0.01). Bacteroidetes dorei and Bacteroides intestinalis were reduced in women with higher SBP CoV ( P <0.05) and nondipping status ( P< 0.01), respectively. Prewaking and sleepthrough MBPS had a positive association with Faecalibacterium prausnitzii in women (all P <0.001) and plasma acetic acid levels in men ( P <0.05-0.001). Further analysis indicated that Bacteroidetes dorei may mediate SBP CoV via plasma iso-butyric acid in women (bootstrapping 95% CI: -3.6 to -0.19; P <0.05). Conclusions: This cross-sectional study suggests sex-specific associations between GM and BP variability. Most noteworthy, higher systolic BP variability was associated with a significant reduction in potentially beneficial bacterial species, primarily in women which may be explored for therapeutic potential.
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