THE ROLE OF GUT MICROBIOME AND HOST METABOLOME IN DIET AND CARDIOVASCULAR RISK FACTORS

Abstract

High blood pressure (BP) and high adiposity are leading risk factors for cardiovascular morbidity and mortality. Excessive sodium, low potassium, and low fiber intake are among the main contributors to elevated BP and adiposity. We hypothesize that the gut microbiota and host metabolites are influenced by diet and have effects on cardiovascular health. Numerous animal model studies have suggested that dietary intake impacts host BP and adiposity particularly through microbiota-mediated short-chain fatty acids (SCFAs). Yet, there is limited empirical evidence in humans to inform current understanding. To address this research gap, we used a cross-sectional adult cohort from the population-based Chinese Health and Nutrition Survey (CHNS) with rich gut microbiota (16S rRNA) and plasma metabolomics data, high-quality diet data from three-consecutive 24-h validated recalls and household food inventories, and health data from physical examinations. We first examined the association between sodium and potassium with gut microbiota and plasma metabolites. We then investigated the associations between gut microbiota and plasma metabolites with systolic (SBP) and diastolic BP (DBP). Last, we assessed the associations between plasma SCFAs and two adiposity measures, body mass index (BMI) and waist-to-height ratio (WHtR). After accounting for geographic variation in microbiota, we found that that sodium and potassium consumption was associated with microbiota and metabolites, including Staphylococcus, microbiota-derived phenolics and SCFAs previously linked to inflammation, hypertension and adiposity. While we did not observe statistical evidence for an association between SCFAs and BP, we found that sphingomyelins, acyl-carnitines, and a lipids pattern characterized by long-chain fatty acids were positively associated with BP. We also found positive associations between SCFAs with BMI and WHtR. Our results suggest that gut microbiota and related metabolites may play an important role in the dietary etiology of cardiovascular disease (CVD). As such, our findings provide insights into potential dietary interventions targeting microbiota or metabolites for disease prevention and treatment. Future longitudinal and randomized-controlled studies are needed to determine the causal relationships between diet, gut microbiome, host metabolome, and CVD risk factors.Doctor of Philosoph

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