Longitudinal associations of the gut microbiome with arterial stiffness in US adults: findings from the Baltimore Longitudinal Study of Aging.

The gut microbiome affects arterial stiffness in experimental murine models; however, evidence in human longitudinal studies is lacking. In this study, we investigated longitudinal between-person (average) and within-person (change) associations of microbiome features with arterial stiffness. We assessed the fecal microbiome using whole genome metagenomic sequencing, and arterial stiffness using carotid-femoral pulse wave velocity (cfPWV). Our analytic sample consisted of 349 adults from the Baltimore Longitudinal Study of Aging, who contributed 915 visits between 2013-2019. Using linear mixed models, we found higher microbiome evenness and butyrate-producing bacteria were associated with lower cfPWV on average (between-person), but changes in diversity were not associated with changes in cfPWV (within-person). Several potentially pathogenic bacteria were positively associated with cfPWV, both between- and within-person. Butyrate-production pathways were inversely associated with cfPWV between-person and borderline within-person. Trimethylamine-production genes were positively associated with cfPWV between-person and borderline within-person. In addition, changes in other functional pathways including peptidoglycan biosynthesis and L-arginine biosynthesis were associated with changes in cfPWV. In conclusion, cfPWV was associated with both between-person and within-person differences in gut microbiome features, with strength and consistency depending on the feature. These results can inform which microbiome features to target in interventions to improve arterial stiffness.