Higher Gut Microbiota Diversity And Abundance Of Butyrogenic Species Are Associated With Lower Pulse Wave Velocity In The Baltimore Longitudinal Study Of Aging

Background: Gut microbiota, particularly butyrogenic species, may affect risk of cardiovascular disease through effects on arterial stiffness. However, studies on gut microbiota and arterial stiffness in human population studies are sparse, with no prior studies having used shotgun metagenomic sequencing to identify species. Objective: To investigate associations of gut microbiota with measures of arterial stiffness as measured by pulse wave velocity (PWV). Methods: We studied 780 adults from the Baltimore Longitudinal Study of Aging who provided feces for shotgun metagenomic microbiome sequencing and at least 1 measure of carotid-femoral PWV between 2013 and 2017. We examined associations of PWV (continuous and as quartiles) with gut microbiome features using beta-binomial and linear regression models for microbiota relative abundances; linear regression models for microbial alpha diversity (Shannon index); and PERMANOVA for microbial beta diversity (Weighted Unifrac distance). We adjusted all models for age, sex and race. We used an FDR-threshold of q <0.05 for abundance models. Results: Approximately 55% of our sample were female and 65% identified as white, with a mean age of 71 years. Microbial beta diversity was significantly associated with PWV (Weighted UniFrac p=0.003, R 2 =0.01), and a 1-SD increase in (Shannon index) alpha diversity was associated with a 0.21 decrease in PWV (p=0.002). Twelve species were associated with continuous PWV, including 4 key butyrate producers in dose-response fashion (Figure). These findings persisted after further adjustment for Mediterranean diet score. Conclusion: Higher microbial diversity and abundance of key butyrogenic bacteria were associated with lower arterial stiffness in a racially diverse cohort of US adults. Some of the species associated with arterial stiffness, e.g. F. prausnitzii and other taxa in Figure, have been previously associated with lower cardiovascular disease risk. Clinical trials are needed to determine if these relationships are causal.