Arterial stiffness—defined as the reduced capability of an artery to expand and contract in response to pressure changes—has been previously reported as an independent predictor of major adverse cardiovascular events in individuals with metabolic syndrome. However, it is poorly associated with traditional cardiovascular risk factors, including hyperlipidemia, diabetes mellitus, obesity and smoking. Furthermore, we do not know whether gut microbiome composition as a new player in inflammation and metabolism may have an impact on arterial stiffness.
A new study, led by Dr. Ana M. Valdes from King’s College London and the University of Nottingham (UK), has found that arterial stiffness is inversely correlated with gut microbiome diversity and the abundance of specific gut microorganisms in women.
In order to examine whether gut microbial composition was associated with arterial stiffness, the researchers measured carotid-femoral pulse wave velocity—defined as the propagation of the pressure wave along the arterial tree related to the intrinsic elasticity of the arterial wall—serum metabolites and gut microbiome composition determined by 16S ribosomal ribonucleic acid in 617 middle-aged women from the TwinsUK cohort.
After adjusting for potential confounders associated with either microbiota changes or arterial stiffness (including lifestyle factors, medication, traditional cardiovascular risk factors, inflammatory markers, visceral fat mass and insulin resistance), pulse wave velocity as a measure of arterial stiffness was negatively correlated with gut microbiome alpha diversity. The findings showed that arterial stiffness was higher in the women who had a lower level of diversity in their gut microbiota.
Indeed, arterial stiffness correlated negatively with specific microbes that were previously related to a lower risk of obesity, that is, seven operational taxonomic units (OTUs), of which two belonged to the Ruminococcaceae family. These associations remained significant after adjustment for levels of gut-derived metabolites that may be involved in arterial aging, such as indolepropionate, trimethylamine-N-oxide (TMAO) and phenylacetylglutamine.
On the other hand, the study quantified the proportion of variation in arterial stiffness, explained by gut microbiome composition and microbiome-derived metabolites when compared with metabolic syndrome-related features. Gut microbiome diversity and circulating levels of the microbiome-derived metabolites phenylacetylglutamine and indolepropionate explained 8.3% of the overall variance in pulse wave velocity. In contrast, insulin resistance and visceral fat only explained 1.8% of the variance in pulse wave velocity. Besides this, the effect of gut microbiome composition on pulse wave velocity was only minimally mediated by metabolic syndrome (metabolic syndrome-related features including insulin resistance, visceral fat, C-reactive protein and traditional cardiovascular risk factors explained 5.51% of the total effect of the gut microbiome on pulse wave velocity).
A substantial proportion of major adverse cardiovascular events are not explained by traditional risk factors, particularly in younger people and in women. According to the researchers, these results open up the gut microbiome’s potential contribution to cardiovascular risk not related to traditional cardiovascular risk factors.
In conclusion, this is the first study that reveals an association between gut microbiome diversity and arterial stiffness in humans. As such, the modulation of the gut microbiome through diet and drugs to improve the commensal gut microbial communities and reduce the risk of heart disease deserves to be explored further.
Menni C, Lin C, Cecelja M, et al. Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J. 2018; 39:2390-7. doi: 10.1093/eurheartj/ehy226.