Essential Hypertension Is Associated With Changes in Gut Microbial Metabolic Pathways: A Multisite Analysis of Ambulatory Blood Pressure

Abstract

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P <0.01), but there was no difference in age between the groups (59.2±7.7 versus 60.3±6.6 years old). Based on machine learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome α- and β-diversity metrics between normotensives versus essential or masked hypertensives. However, select taxa were specific to these groups, notably Acidaminococcus spp ., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. 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 short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites.

The Gut Microbiome and their Metabolites in Human Blood Pressure Variability

“…53 Here we identified a negative association between BP SD and night-time dipping and GPR43 in circulating immune cells. This is consistent with our previous findings regarding 24-h systolic BP 20 and aortic stiffness, 54 suggesting a blunted response to BP-lowering metabolites.…”

“…23 The quality of participants’ diet was also measured as Australian Dietary Guideline Index (DGI-2013) 24,25 as described previously. 20,26…”

“…This study followed guidelines for gut microbiota studies in hypertension 27 and the Strengthening the Organization and Reporting of Microbiome Studies (STORMS) reporting 28 (checklist available at 20 ). Sample collection, DNA extraction, library preparation and sequencing were described in detail previously.…”

“…Sample collection, DNA extraction, library preparation and sequencing were described in detail previously. 20 Briefly, DNA from the stool samples was extracted using the DNeasy PowerSoil DNA isolation kit (Qiagen). The V4-V5 region of the bacterial 16S rRNA was amplified by PCR using the Earth Microbiome Project 29 protocol.…”

“…Briefly, plasma SCFAs were measured in 200 µL and faecal SCFAs were measured from 1 g of faecal sample, all in triplicates, as previously published, 20 in an Agilent GC6890 coupled to a flame-ionisation detector. 35,36 A coefficient of variation of <10% within triplicate samples was used as a quality control measure.…”