Background and Objective: Our goal was to examine the previously unknown long-term association between gut microbiome composition and incident hypertension in a representative population cohort. Methods: We collected fecal samples from a population sample of 3,055 non-hypertensive Finns (mean age 43.1 years; 60.8% women) in 2002. These individuals were followed up for incident hypertension until 31 December 2021 using nationwide register data. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident hypertension using Cox regression (alpha diversity and microbial taxa), permutational multivariate ANOVA (beta diversity) and Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC; microbial taxa) models adjusted for conventional hypertension risk factors. Results: Altogether, 587 cases of incident diabetes occurred over the median follow-up of 19.8 years. Gut microbiome alpha diversity (Shannon index; p=0.98) and beta diversity (R2=0.49%; p=0.99) were not associated with incident hypertension. Furthermore, the associations between microbial taxa and incident hypertension were non-significant. In Cox regression models (Figure), two species reached an FDR-corrected P-value <0.1: Eubacterium G Ventriosum (hazard ratio per 1-SD increase 0.89; 95% CI 0.83-0.96; P=0.07) and Hespellia Stercorisuis (hazard ratio 1.16; 95% CI 1.05-1.27; P=0.098). In ANCOM-BC models, three species reached an FDR corrected P-value of <0.1: Merdousia sp000438015 (log2 fold change 0.32±0.09; P=0.06), Mitsuokella multacida (log2 fold change -0.32±0.09; P=0.06), and Scybalousia sp900543675 (log2 fold change -0.28±0.09; P=0.07). Conclusions: In this first-ever analysis on the association between the gut microbiome and long-term hypertension incidence, we observed that the associations between overall gut taxonomic composition and incident hypertension are weak. In addition, only a few microbial taxa reached a borderline level of significance with inconsistent results between two statistical methods. These findings suggest that the gut microbiome is not a strong predictor of future hypertension.
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