Relationship between pesticide exposure, gut microbiota, and hypertension

BACKGROUND: Both pesticide exposure and gut dysbiosis have been independently linked to an elevated risk of hypertension. However, the extent of interaction between these two factors remains poorly characterized in human populations. METHODS: In a population-based study involving 218 adults from Jiangsu Province, China, we quantified pesticides in serum using LC-MS/MS and analyzed the gut microbiome via metagenomic sequencing. An environmental risk score (ERS) was created to represent pesticide exposure. We also used Mendelian randomization (MR) to identify causal gut microbial genera, multivariable regression for associations, and mediation analysis for potential pathways. Machine learning models were applied to differentiate hypertensive from non-hypertensive individuals based on a combined set of features. RESULTS: Fourteen pesticides, notably bentazone and perfluorohexanesulfonate, were significantly associated with increased hypertension risk, and the ERS based on these pesticides further corroborated this association. Additionally, the overall microbiota composition was significantly associated with both pesticide exposure and hypertension status. Observational and MR analyses consistently identified branches of Clostridium as potentially contributors to hypertension risk. An interaction was observed between pesticide exposure and specific bacterial taxa. Specifically, high ERS combined with high Catenibacterium (both defined using a median split) abundance increased hypertension risk nearly fourfold. A neural network model achieved the best differentiation performance (AUC = 0.897) for hypertension. CONCLUSIONS: Exposure to specific pesticides, particularly bentazone, is associated with increased hypertension risk. This relationship is influenced by interactions with gut bacteria and partially mediated through alterations in the gut microbiota. These findings highlight the role of environmental chemicals and the gut microbiome in the development of hypertension.