Gut Microbiota-Derived Trimethylamine N-Oxide (TMAO) and Its Association with Atherosclerotic Burden in Vegetarian versus NonVegetarian Populations: A Cross-Sectional Study

Background: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been associated with cardiovascular disease and atherosclerotic burden. Dietary patterns may influence circulating TMAO concentrations through differences in the availability of substrates for microbial trimethylamine production; however, the relationship between dietary pattern, TMAO, and subclinical atherosclerosis remains incompletely understood. This study aimed to compare circulating TMAO concentrations and carotid atherosclerotic measures, including carotid intima-media thickness (CIMT) and carotid plaque, between vegetarian and non-vegetarian adults and to assess the association between TMAO concentration and atherosclerotic burden. Methods: An analytical cross-sectional study was conducted among 200 adults, comprising 100 vegetarian and 100 non-vegetarian participants. Demographic, clinical, anthropometric, dietary, and lifestyle data were collected using a structured questionnaire. Blood samples were analyzed for TMAO, lipid profile, glucose parameters, and renal function. Carotid ultrasonography was performed to assess CIMT and carotid plaque. Associations between TMAO and CIMT were evaluated using correlation and multivariable linear regression, while binary logistic regression was used to assess the association between TMAO and carotid plaque after adjustment for relevant cardiovascular risk factors. Results: Mean TMAO concentration was significantly higher among non-vegetarians than vegetarians (4.21 ± 2.05 vs 2.86 ± 1.34 µmol/L; p<0.001). Mean CIMT was also higher in non-vegetarians (0.69 ± 0.11 vs 0.62 ± 0.09 mm; p<0.001). Carotid plaque was present in 27.0% of non-vegetarians compared with 14.0% of vegetarians (p=0.022). TMAO showed a positive correlation with mean CIMT (r=0.38; p<0.001). After multivariable adjustment, each 1 µmol/L increase in TMAO was associated with a 0.018-mm increase in mean CIMT (adjusted β=0.018; 95% CI: 0.010–0.026; p<0.001) and higher odds of carotid plaque (adjusted OR=1.42; 95% CI: 1.13–1.78; p=0.002). TMAO concentrations were also associated with total cholesterol and LDL-C. Conclusion: In this cross-sectional study, non-vegetarian participants had higher circulating TMAO concentrations, greater CIMT, and a higher prevalence of carotid plaque than vegetarian participants. Higher TMAO concentrations were positively associated with CIMT and carotid plaque after adjustment for relevant cardiovascular risk factors. These findings support an association between circulating TMAO and subclinical atherosclerotic burden; however, the cross-sectional design does not establish causality.