ObjectiveThe gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.DesignA pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.ResultsThe OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.ConclusionThe OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.Trial registration numberNCT02838732; Results.

Background/objectivesVegetarian diets are inversely associated with diabetes in Westerners but their impact on Asians—whose pathophysiology differ from Westerners—is unknown. We aim to investigate the association between a vegetarian diet, change in dietary patterns and diabetes risk in a Taiwanese Buddhist population.MethodsWe prospectively followed 2918 non-smoking, non-alcohol drinking Buddhists free of diabetes, cancer, and cardiovascular diseases at baseline, for a median of 5 years, with 183 incident diabetes cases confirmed. Diet was assessed through a validated food frequency questionnaire at baseline and a simple questionnaire during follow-ups. Incident cases of diabetes were ascertained through follow-up questionnaires, fasting glucose and HbA1C. Stratified Cox Proportional Hazards Regression was used to assess the effect of diets on risk of diabetes.ResultsConsistent vegetarian diet was associated with 35% lower hazards (HR: 0.65, 95% CI: 0.46, 0.92), while converting from a nonvegetarian to a vegetarian pattern was associated with 53% lower hazards (HR: 0.47, 95% CI: 0.30, 0.71) for diabetes, comparing with nonvegetarians while adjusting for age, gender, education, physical activity, family history of diabetes, follow-up methods, use of lipid-lowering medications, and baseline BMI.ConclusionVegetarian diet and converting to vegetarian diet may protect against diabetes independent of BMI among Taiwanese.

IntroductionVegetarian diets have been shown to improve glucose metabolism and reduce risk for diabetes in Westerners but whether Chinese vegetarian diets have the same benefits is unknown.MethodsWe evaluated the association between diet and diabetes/impaired fasting glucose (IFG) among 4384 Taiwanese Buddhist volunteers and identified diabetes/IFG cases from a comprehensive review of medical history and fasting plasma glucose.ResultsVegetarians had higher intakes of carbohydrates, fiber, calcium, magnesium, total and non-heme iron, folate, vitamin A, and lower intakes of saturated fat, cholesterol, and vitamin B12. Besides avoiding meat and fish, vegetarians had higher intakes of soy products, vegetables, whole grains, but similar intakes of dairy and fruits, compared with omnivores. The crude prevalence of diabetes in vegetarians versus omnivores is 0.6% versus 2.3% in pre-menopausal women, 2.8% versus 10% in menopausal women, and 4.3% versus 8.1% in men. Polytomous logistic regression adjusting for age, body mass index, family history of diabetes, education, leisure time physical activity, smoking and alcohol, showed that this vegetarian diet was negatively associated with diabetes and IFG in men (OR for diabetes: 0.49, 95% CI: 0.28–0.89; OR for IFG: 0.66, 95% CI: 0.46–0.95); in pre-menopausal women (OR for diabetes: 0.26, 95% CI: 0.06–1.21; OR for IFG: 0.60, 95% CI: 0.35–1.04); and in menopausal women (OR for diabetes: 0.25, 95% CI: 0.15–0.42; OR for IFG: 0.73, 95% CI: 0.56–0.95).ConclusionWe found a strong protective association between Taiwanese vegetarian diet and diabetes/IFG, after controlling for various potential confounders and risk factors.