Gut microbiome diversity and composition is associated with hypertension in women.

ABSTRACT

OBJECTIVES: Animal studies support a role for the gut microbiota in hypertension development, but large human studies are lacking. Here, we investigated the relationship between hypertension prevalence and gut microbial composition in two cohorts. METHODS: We included 871 unrelated TwinsUK women with faecal microbiome data (16s rRNA gene sequencing). Multivariable linear models adjusted for age, age2 and BMI as well as MiRKAT models, were used to estimate the association of hypertension with alpha- and beta-diversity metrics. To identify taxa associated with hypertension, a generalized additive model for location scale and shape was computed adjusting for covariates and multiple testing. Results were replicated in 448 women from PREDICT-1. RESULTS: We found that measures of alpha diversity are significantly lower in hypertensive cases [Beta(95% confidence interval, 95% CI) = -0.05 (-0.095 to -0.004), P = 0.03] and a significant association between beta diversity and hypertension (FDR < 0.05). We identified and replicated two genera associated with hypertension. The genus, Ruminiclostridium 6 was less abundant in hypertension cases [meta-analysis (95% CI) = -0.31 (-0.5 to -0.13), P = 1 × 10-3]. The uncultured microbe Erysipelotrichacea-UCG003 was more abundant in hypertensive cases [meta-analysis (95% CI) = 0.46 (0.3-0.62), P = 1 × 10-4]. We genomically analysed the 16 s rRNA sequence and established a 100% identity match with the 16 s rRNA sequence of the genus Faecalibacillus. We functionally annotated Ruminiclostridium, identifying 83 metabolic pathways, including pathways previously linked to blood pressure regulation. CONCLUSION: In this large human observation, we show that gut microbiome diversity and composition are associated with hypertension. Our results suggest that targeting the microbiome may be a novel means to prevent or treat hypertension.