Genetic association between gut microbiome and blood pressure and blood cell count as mediator: A two-step Mendelian randomization analysis

Abstract

BackgroundPrevious studies have established a genetic link between gut microbiota and hypertension, but whether blood cell count plays a mediating role in this remains unknown. This study aims to explore genetic associations and causal factors involving the gut microbiome, peripheral blood cell count, and blood pressure. MethodsWe utilized summary statistics derived from genome-wide association studies to conduct a two-sample mediation Mendelian randomization analysis (https://gwas.mrcieu.ac.uk/). We applied inverse variance weighted (IVW) estimation method as the primary method, along with MR Egger, Weighted median, Simple mode and Weighted mode as complementary methods. To ensure the robustness of the results, several sensitivity analyses were conducted. ResultsGenetic variants significantly associated with the microbiome, blood pressure, or peripheral blood cell counts were selected as instrumental variables. Fourteen microbial taxa were found to have suggestive associations with diastolic blood pressure (DBP), while fifteen microbial taxa showed suggestive associations with systolic blood pressure (SBP). Meanwhile, red blood cell count, lymphocyte count, and platelet count were identified to mediate the influence of the gut microbiome on blood pressure. Specifically, red cell count was identified to mediate the effects of the phylum Cyanobacteria on DBP (mediated proportion: 8.262 %). Lymphocyte count was found mediate the effects of the genus Subdoligranulum (mediated proportion: 2.642 %) and genus Collinsella (mediated proportion: 2.749 %) on SBP. Additionally, platelet count was found to mediate the relationship between the genus Eubacterium ventriosum group and SBP, explaining 3.421 % of the mediated proportion. ConclusionsOur findings highlighted that gut microbiota may have causal influence on the blood pressure by modulating blood cell counts, which sheds new light on the pathogenesis and potential clinical interventions through the intricate axis of gut microbiome, blood cell counts, and blood pressure.