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

Abstract

Abstract 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.