Abstract

AimsThe gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness.Methods and resultsWe assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= −0.25(0.07), P = 1 × 10−4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing—two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3–12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure.ConclusionsGut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.

Highlights

  • A substantial proportion of major adverse cardiovascular events (MACE) within the population are not explained by traditional cardiovascular risk factors

  • Gut microbiome diversity is inversely associated with arterial stiffness in women

  • We investigated whether any association between arterial stiffness and the microbiome might be accounted for by specific circulating metabolites known to be generated by the gut microbiome: phenylacetylglutamine and trimethylamine oxide (TMAO), previously linked to cardiovascular disease,[2] and indoleproprionate (IPA),[21] an antioxidant associated with metabolic syndrome (MetS),[22] and which might influence arterial stiffness

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Summary

Introduction

A substantial proportion of major adverse cardiovascular events (MACE) within the population are not explained by traditional cardiovascular risk factors.

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