Essential hypertension is associated with changes in gut microbial metabolic pathways: A multi-site analysis of ambulatory blood pressure
AbstractAimsRecent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure (BP) is associated with gut microbiota and their metabolites remains unclear. Here we characterised the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in metropolitan and regional areas of Australia.Methods and ResultsAmbulatory BP, faecal microbiome DNA 16S rRNA gene sequencing, plasma and faecal metabolites called short-chain fatty acid (SCFAs), and expression of their receptors were analysed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Based on machine-learning multivariate covariance analyses of de-noised amplicon sequence variant (ASV) prevalence data, we determined that there were no significant differences in gut microbiome community α- and β-diversity metrics between normotensives versus essential, white coat or masked hypertensives. However, select taxa were specific to these groups, notably Acidaminococcus spp. in essential hypertensives, and Ruminococcus spp. and Coprobacillus in normotensive subjects. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of SCFA-activated G-protein coupled receptor 43 (GPR43).ConclusionsWhile gut microbial diversity did not change in essential hypertension, there was a significant shift in microbial gene pathways, and an increase in the circulating levels of the SCFAs acetate and butyrate. Hypertensive subjects, however, had lower levels of the SCFA-sensing receptor GPR43, putatively blunting their response to BP-lowering metabolites.