Association between gut microbiota and vascular ageing in a multi-ethnic population: the HELIUS Study

Abstract Introduction Vascular ageing (VA), characterised by arterial stiffness (AS) and endothelial dysfunction, is a major contributor to cardiovascular disease (CVD), yet its early detection is challenging. Emerging evidence suggests that gut microbiota (GM) influences VA, but studies in diverse populations remain scarce. Purpose To assess the association between GM composition and VA markers, focusing on sex- and ethnicity-specific differences. Methods This cross-sectional study included 2,532 participants from the multi-ethnic HEalthy Life In an Urban Setting (HELIUS) cohort. Microbiome composition was assessed using 16S rRNA sequencing of stool samples. VA markers (aortic pulse wave velocity (AoPWV), central systolic blood pressure (cSBP), and augmentation index (AIx)) were measured using validated techniques. Alpha diversity was evaluated using the Shannon index, while beta diversity differences between groups were assessed with the PERMANOVA test on Bray-Curtis distances. Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) was used to identify differentially abundant genera, which were analysed in adjusted linear and logistic regression models, including sex and ethnicity interactions. Results VA markers significantly differed by ethnicity, with Dutch participants showing the most favourable profiles, while Surinamese and Ghanaian groups exhibited the worst. Beta diversity differed across all VA markers (p 0.001), while alpha diversity was only significant for cSBP (p 0.001). At the genus level, Faecalibacterium, Coprococcus 3, and Ruminococcaceae UCG-013 abundance were linearly associated with lower AoPWV (Figure 1), while Streptococcus increased AoPWV and AIx. Anaerostipes showed a protective effect on AoPWV only in men, while Dorea was associated with lower cSBP only in women. In logistic models (Figure 2), Bacteroides and Faecalibacterium reduced the odds of AS by 10% (95%CI: 0.82,0.99) and 11% (95%CI: 0.81,0.99), respectively, while Streptococcus increased the odds of AS by 8% (95%CI: 1.01,1.16). Lachnospiraceae UCG-010, Marvinbryantia, and Ruminococcaceae UCG-003 were protective against high cSBP (OR=0.86, 95%CI: 0.77,0.95; OR=0.87, 95%CI: 0.77,0.99; OR=0.82, 95%CI: 0.70,0.95, respectively). Notably, Lachnospiraceae UCG-010 and Ruminococcaceae UCG-013 were protective against AS and high cSBP in men. Ethnic-specific effects were observed, with Ruminococcaceae UCG-013 reducing AS and AIx in South-Asian Surinamese and high cSBP in Moroccans. Conclusions GM composition is associated with VA, with notable differences across sex and ethnic groups. Our findings underscore the need for personalised approaches when considering microbiome-based interventions in diverse populations. Longitudinal studies are needed to clarify causal relationships and assess the clinical potential of microbiome-targeted interventions.Linear associations between taxa and VA Logistic associations - taxa and VA