Hypertension and gut microbial hydrogenases: a comparison of hydrogen metabolism and etiology

Hypertension is a prevalent chronic condition and serves as a significant risk factor for numerous cardiovascular and cerebrovascular disorders. Gut microbiota dysbiosis has been considered to contribute to the pathogenesis of hypertension. It has been reported that a large majority of gut microbiota possess genes encoding hydrogenases. These hydrogenases are involved in the alteration of gut microbiota in non-infectious colitis, suggesting a potential link between microbial hydrogen metabolism and disease onset. This study aims to explore the relationship between hydrogenase expression patterns in the gut microbiome and the incidence of hypertension. In this study, publicly available gut microbiome metagenomic data were used to comprehensively analyze the expression patterns of hydrogenases in the gut microbiota of hypertensive patients. Compared with the control group, a 2.3-fold increase in electron bifurcating [FeFe] group A3 hydrogenases (P = 0.0299), a 55.6% decrease in [NiFe] group 1d hydrogenases (P = 0.0097), increased hydrogen-sensing hydrogenases and decreased hydrogen-uptake hydrogenases in the hypertension group. The main difference between the two groups is reflected in the abundance of [NiFe] hydrogenase subtypes. After eliminating the effects of factors such as age, sex, and lifestyle, significant differences in the abundance of [FeFe] group A3, [NiFe] group 1d, and [NiFe] group 1c were observed between the two groups, suggesting that these three indicators could serve as potential biomarkers for diagnosing the onset of hypertension. Additionally, Mendelian randomization analysis showed a protective effect of hydrogen metabolism against hypertension (odds ratio = 0.72, 95% confidence interval: 0.61-0.85, P < 0.001). Our study advances the understanding of microbiome-mediated mechanisms in hypertension by demonstrating an association between hydrogenase expression dynamics and blood pressure regulation, providing a foundation for future microbiome-based diagnostic and therapeutic strategies.