Plasma biomarkers of dairy intake and gut microbiome, and their association with incident carotid plaque: a prospective cohort study.

BACKGROUND

This study aimed to investigate the prospective association of dairy biomarkers of odd-chain saturated fatty acids (OCFA) with incident carotid artery plaque (CAP) and to explore the potential role of gut microbiota and related metabolites in the above associations.

METHODS

In the Guangzhou Nutrition and Health Study (GNHS, n = 1211; baseline mean age: 58.7 ± 6.1 years), we investigated the associations of baseline plasma phospholipid OCFAs with CAP incidence and gut microbiota (16S rRNA sequencing) over a median follow-up period of 6.2 years. Westlake Precision Birth Cohort was used to evaluate the potential associations between OCFA and the identified gut microbiota features in a younger population. Associations of OCFAs with CAP, gut microbial alpha diversity, specific genera, and related metabolites were examined using Cox proportional hazards models or linear regression models, with adjustments of potential confounders.

RESULTS

The total OCFA was inversely associated with the incidence of CAP in the GNHS, with a hazard ratio of 0.63 (quartile 4 versus 1: 95% confidence interval [CI]: 0.46, 0.86). Additionally, total OCFA was significantly associated with gut microbial alpha and beta diversity (all P < 0.05). The beta coefficient for the association between total OCFA and the Shannon index was 0.11 (95% CI: 0.06, 0.17). We identified 36 microbial genera significantly associated with total or individual OCFAs (FDR < 0.05). Among these identified genera, the Christensenellaceae R-7 group, an OCFA-positive-related genus, was inversely associated with the prevalence of CAP (P < 0.05). We then identified 13 microbe-derived metabolites significantly associated with both total OCFA and C. R-7 group (FDR < 0.05), including deoxycholic acid and lithocholic acid.

CONCLUSIONS

Our results suggest that plasma OCFAs, as objective biomarkers of dairy exposure, are inversely associated with CAP incidence in a Chinese cohort. Further exploration indicates that gut microbiota may be involved in the above association, providing a potential gut microbiota-based intervention target for atherosclerosis.