Gut microbiome diversity is inversely associated with arterial stiffness
Gut microbial diversity is associated with lower arterial stiffness in women
Literature - Menni C, Lin C, Cecelja M, et al. - Eur Heart J 2018;39:2390–2397Introduction and methods
The gut microbiome, an important regulator of systemic inflammation, glucose tolerance, and insulin sensitivity, may influence vascular disease through oxidative stress and inflammation [1]. Arterial stiffness, measured by pulse wave velocity (PWV), is an independent predictor of CV risk [2]. Inflammation contributes to the development of arterial stiffness. Therefore, a relationship between gut microbiome composition and arterial stiffness was hypothesized.
In this study, the association between arterial stiffness and gut microbiome composition was evaluated, by examining relationships between PWV and microbiome diversity, as well as between PWV and specific operational taxonomic units (OTUs). Moreover, it was assessed whether the associations between arterial stiffness and the microbiome are mediated by the specific circulating metabolites phenylacetylglutamine, trimethylamine oxide (TMAO), and the antioxidant indoleproprionate (IPA).
For this purpose, data from 617 female twins aged 40-79 years were analyzed, who were included in the TwinsUK registry [3,4]. Those eligible for the analysis had PWV and serum metabolites measurements, as well as gut microbiome composition determined by 16S rRNA gene sequencing. The 10-year atherosclerotic CV disease (ASCVD) risk was calculated based on age, gender, total and high density lipoprotein cholesterol, smoking status, blood pressure (BP) and use of BP-lowering medications, as well as type 2 diabetes (T2DM).
Main results
- Indices of gut microbiome diversity were significantly associated with PWV (Shannon: Beta = -0.26±0.07; P=9x10-5, Simpson: Beta = -0.18±0.07; P=10-3) after adjusting for age, body mass index (BMI), mean arterial BP, and family relatedness.
- Seven OTUs were significantly and negatively associated with PWV (false discovery rate < 0.05): two from the Ruminococcaceae family, one from the Rikenellaceae and one from the Clostridiaceae, one from the Barnesiellaceae family, one of the Clostridiaceae family, and the genus Odoribacter.
- After adjusting for smoking, alcohol intake, physical activity, fiber and omega 3 intake, adherence to a Mediterranean diet, socioeconomic status, proton pump inhibitors, antibiotics use, uric acid, the 10-year ASCVD risk score, and CRP levels, the results remained consistent.
- PWV remained significantly associated with gut microbiome composition after adjusting for visceral fat mass and insulin resistance, with each standard deviation of the microbial abundances contributing an effect size of -0.12 to -0.27 on PWV (P values ranging from 0.002 to 3x10-5).
- The associations between PWV and gut microbiome diversity and specific OTUs were attenuated after adjustment for phenylacetylglutamine, TMAO, and the antioxidant IPA, but remained significant. After adjusting for age, BMI, and mean arterial BP, the overall proportion of variance explained by microbiome factors is 8.3% (95%CI: 4.32–12.4%).
Conclusion
In a study of middle-aged female twins, the composition of the gut microbiome was strongly correlated with arterial stiffness, independently of traditional risk factors. These data suggest that targeting the gut microbiome with specific therapies might improve arterial stiffness.
Editorial comment
In their editorial article, Laurent and Bruno [5] emphasize the most important finding of the study by Menni et al.: arterial stiffness is significantly correlated with gut microbiome, and this association is only marginally mediated by a large number of traditional risk factors. Although age and mean BP can explain up to 50% of arterial stiffness, the authors comment positively on the finding of gut microbiome being able to explain 4-8% of the arterial stiffness variance. They also discuss the limitations of the study, including the lack of endotoxemia markers measurements, the fact that dietary fats were not explored, the cross-sectional study design, and the homogeneity of the study sample, composed of middle-aged female twins. The authors conclude: ‘… the study by Menni et al. provides a valuable contribution to the ongoing research on the relationship between arterial stiffness and inflammation. The authors demonstrated that it was possible to capture, through the characterization of the gut microbiome, a part of the CV risk that was not explained by classical risk factors. These data suggest that the gut microbiome may act as a third player in the inflammation–stiffness relationship.’