Gut microbiota-associated metabolite trimethylamine N-oxide and the risk of stroke: a systematic review and dose-response meta-analysis
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AIMS: Several epidemiological studies have examined the association between trimethylamine N-Oxide (TMAO) and stroke risk; however, the results are still inconclusive. The purpose of this meta-analysis was to evaluate the relationship between TMAO concentrations and stroke risk. METHODS: PubMed, Scopus, Cochrane and ProQuest search engines were systematically searched up to 18 June 2019. All of the studies that evaluated the relationship between TMAO and stroke were included in the systematic review and eligible studies were included into the meta-analysis. Meta-regression and subgroup analysis were also employed to find the source of heterogeneity. RESULTS: Eight studies (two cross-sectional studies, two cohort studies, three case-control studies and one nested case-control study) with a total of 6150 participants were included in the meta-analysis. The overall result showed that being in the highest category of TMAO increased the odds of stroke by 68% (OR: 1.675; CI: 0.866-3.243; P = 0.047) and mean TMAO concentrations was 2.201 μmol/L higher in patients with stroke rather than non-stroke controls (weighted mean difference (WMD): 2.20; CI: 1.213-3.188; P < 0.001). Furthermore, we observed revealed a non-linear association between increased TMAO levels and increased odds of stroke (P- for nonlinearity < 0.001). In addition, visual inspection of the funnel plot revealed a significant asymmetry among studies examining the differences in TMAO in patients with stroke versus control group. CONCLUSION: This is the first meta-analysis to show positive dose-dependent relations between circulating TMAO concentration and stroke risk. However, further interventional studies and long-term studies are needed to better explain causality.
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Trimethylamine (TMA) is produced by microbial metabolism from dietary choline, and once absorbed, TMA is converted to TMAO, which has been implicated in various chronic diseases, especially those related to the circulatory system.
“Lastly, a large research focus has also been placed on the microbial production of trimethylamine (TMA) from dietary choline.Once absorbed, TMA is converted to TMAO, which has been implicated in various chronic diseases, especially those related to the circulatory system [e.g., stroke (386)].”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [386]
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- Authors
- Farhangi, M. A., Vajdi, M., & Asghari-Jafarabadi, M.
- Affiliations
- Tabriz University of Medical Sciences (IR)
- Corresponding author
- Farhangi, Mahdieh Abbasalizad
- Venue
- Nutrition Journal
- Published
- 2020-07-30
- Volume
- 19
- Issue
- 1
- Pages
- 76-76
- ISSN
- 1475-2891 (ISSN-L)
- PMC
- PMC7393891
- OpenAlex
- W3045741151
- Cited by
- 72
- References
- 73
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 10 · 2023: 16 · 2022: 19 · 2021: 10 · 2020: 2
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nutrition Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Tabriz University of Medical Sciences
- University of Tabriz
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- trimethylamine N-oxide, stroke risk, gut microbiota, metabolites, dose-response relationship, nonlinear relationship, circulating biomarkers
- MeSH terms
- Gastrointestinal Microbiome, Cross-Sectional Studies, Humans, Methylamines, Risk Factors, Case-Control Studies, Stroke
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