Gut microbial diversity is associated with lower arterial stiffness in women

Abstract

Aims: The 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 results: We 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.

Conclusions: Gut 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.

Figure 1

Microbes associated between pulse wave velocity and gut bacterial operational taxonomic units (false discovery rate < 0.1) adjusting for (i) age, body mass index, mean arterial blood pressure and family relatedness, (ii) age, body mass index, mean arterial blood pressure, fibre intake, omega 3 intake, adherence to a Mediterranean diet, and family relatedness, (iii) age, body mass index, mean arterial blood pressure, smoking, alcohol drinking habits, physical activity, PPI, antibiotics use, social deprivation status, and family relatedness, (iv) age, body mass index, mean arterial blood pressure, homeostasis model assessment-estimated insulin resistance, visceral fat mass, and family relatedness, (v) age, body mass index, mean arterial blood pressure, 10-years atherosclerotic cardiovascular disease risk score, c-reactive protein, and family relatedness.

Figure 2

Mediation analysis of the association between (A) microbiome factors and (B) Shannon diversity and pulse wave velocity using partial least squares structural equation modelling. Path coefficients are denoted beside each path and indirect effect and variance accounted for (variance accounted for) score is denoted below each mediator (*P < 0.05; **P < 0.01; ***P < 0.001).

Take home figure

The gut microbiome is related to metabolic syndrome and inflammation, is modifiable via diet, medication and probiotics. Arterial stiffness (measured by pulse wave velocity) is a predictor of major cardiovascular events, which is related to metabolic syndrome and inflammation but poorly correlated with most traditional risk factors other than mean arterial pressure. The hypothesis of this study was that the gut microbiome composition could be related to arterial stiffness. This was measured in 617 women and both specific microbes and gut microbiome diversity, a measure of gut dysbiosis, along with metabolites generated by the gut microbiome were found to be associated with arterial stiffness. In fact, the microbiome related factors explain 8.3% of the variance in pulse wave velocity compared with only 1.8% of insulin resistance combined with visceral fat. These data indicate a strong contribution of the gut microbiome to risk of arterial stiffness and suggest targeting the gut microbiome composition as a therapeutic strategy.