Gut microbiota–associated trimethylamine<i>N</i>-oxide and increased cardiometabolic risk in adults: a systematic review and dose-response meta-analysis
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.004 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".