Mir Mohammad Ali, Seyedeh Nooshan2023-04-112023-04-11https://hdl.handle.net/2097/42978Background: Several studies have shown that diets rich in unprocessed plant-based foods are associated with positive health outcomes, whereas diets rich in animal-source foods are associated with increased incidence of some chronic diseases including metabolic syndrome (MetS). Gut microbiota metabolites, particularly Trimethylamine N-Oxide (TMAO) have recently been identified as potential mechanisms for increased MetS risk. Therefore, the aims of the current study were to investigate the associations between plant-based dietary intake as compared with animal-source dietary intake, and MetS incidence, with a potential mediation role for TMAO. Methods: The Multiethnic Ethnic Study of Atherosclerosis (MESA) dataset was used to conduct a longitudinal secondary analysis to meet our stated aims. The Plant-based Dietary Index (PDI) scoring system was used to score the MESA food frequency questionnaire (FFQ) according to four different indices (PDI), healthy (hPDI), unhealthy (uPDI), animal-source (ADI). We used a Cox proportional hazards mixed effects model to predict the incidence of MetS, and a linear regression model to perform mediation analysis for the potential mediation role of TMAO. Results: The MESA cohort of 5,870 adults aged 45–84 years, of whom 2,449 were diagnosed with MetS at exam 1. Excluding those who had MetS, after 18 years, at exam 6, 1,673 of the 4,582 remaining participants had MetS. Cox proportional hazard mixed effects models examining the effects of PDI, hPDI, and uPDI on incident MetS demonstrated a significant effect for PDI (HR = 0.93, p = 0.03). Mediation analysis with PDI as an independent variable, indicated demonstrated a significant indirect effect for TMAO ([beta] = -0.0002, p = 0.002) on incident MetS, with no significant direct effect ([beta] = -0.001, p = 0.36). Conclusion: These preliminary results suggested that high plant-based dietary intake, decreased the risk of MetS at exam 6, indicating a protective effect for a plant-based dietary pattern when controlling for other factors that might have an effect on incident MetS. The TMAO mediation analysis indicated that the effect of PDI on incident MetS was reduced, suggesting that higher TMAO levels diminished the positive effects of PDI.en-USMetabolic syndromeGut microbiota metaboliteDietary patternPlant-based dietThesis