Gut microbiota-associated trimethylamine N-oxide and increased cardiometabolic risk in adults: a systematic review and dose-response meta-analysis

Context: Several studies suggest a relationship between trimethylamine N-oxide (TMAO) concentrations and increased cardiometabolic risk, but findings are controversial.

Objective: The aim of this systematic review and meta-analysis was to summarize evidence of the relationship between circulating TMAO levels and risk of hypertension and increased serum lipids in a dose-response and 2-class meta-analysis of discrete and continuous variables.

Data sources: PubMed, Scopus, Cochrane, and ProQuest databases were searched.

Study selection: Observational studies that reported disease status of participants (≥ 18 years), type of sample in which TMAO was measured (serum or plasma), and results based on at least 2 categories of TMAO concentrations, including relative risks, hazard ratios, or odds ratios with 95%CIs for cardiometabolic risk factors in association with circulating TMAO levels were selected. Papers were reviewed independently by both authors. The Newcastle-Ottawa Scale was used to assess the quality of included studies.

Data extraction: The following data were extracted: first author's name, publication year, study design, study location, demographic information of participants, and concentrations of circulating TMAO.

Results: Eighteen studies were included in the meta-analysis. There was a dose-response relationship between circulating TMAO and increased odds of hypertension in cohort studies (P for nonlinearity = 0.049), in plasma-derived TMAO samples (P for nonlinearity = 0.043), in patients with cardiovascular disease (P for nonlinearity = 0.048), and in apparently healthy individuals from community-based studies (P for nonlinearity = 0.005). Moreover, the highest category of TMAO concentrations was associated with a 2.36 mmHg increase in systolic blood pressure when compared with the lowest category. The dose-response meta-analysis of continuous variables revealed that an increase in TMAO is associated with reduced high-density lipoprotein cholesterol in apparently healthy individuals and reduced high-density lipoprotein cholesterol and increased total cholesterol in patients with cardiovascular disease.

Conclusions: Circulating TMAO is positively associated with an increased risk of hypertension and other cardiometabolic disorders in adults.

Systematic review registration: PROSPERO identification number CRD42019138296.