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Significant correlation between the gut microbiota-derived metabolite trimethylamine-N-oxide and the risk of stroke: evidence based on 23 observational studies

Abstract

The gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is regarded as a major risk factor for cardiovascular events and diabetes. However, the association of TMAO with stroke has yet to be fully elucidated. The present meta-analysis was conducted to explore the association between TMAO and stroke. The present meta-analysis quantitatively summarized the results of studies that investigated the association between TMAO and stroke. The PubMed, Embase, Cochrane Library and Web of Science databases were systematically searched from January 1, 2001 to June 1, 2021. All studies that evaluated the association between TMAO and stroke were included in the present systematic review. The present meta-analysis included 30,808 participants and revealed that being in the higher TMAO category increased the odds of stroke by 68% (OR 1.83; 95% CI 1.02–3.29; P = 0.04), and that the mean TMAO concentration in stroke patients was 2.20 μmol/L higher than that of non-stroke controls (MD 2.20; 95% CI 1.23–3.16; P < 0.00001). In addition, TMAO plasma levels was associated with the risk of all-cause mortality, with a pooled HR of 1.89 (95% CI 1.15–3.08; P = 0.01). Both univariate analysis (UVA) and multivariate analysis (MVA) indicated that high TMAO levels significantly increased the risk of major adverse cardiovascular events (MACEs), with pooled RRs of 2.26 (95% CI 2.01–2.54; P < 0.00001) with UVA and 1.55 (95% CI 1.17–2.05; P = 0.002) with MVA respectively. In the current meta-analysis we revealed the positive association between circulating TMAO and stroke. Higher TMAO levels increased the risk of stroke and stroke patients experienced higher mean TMAO concentration. In addition, high TMAO plasma level was one of independent risk factors of MACEs and was associated with all-cause mortality.

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Fig. 1: Flow diagram following the PRISMA template of the search strategy for the correlation between Gut Microbiotaderived Metabolite TMAO and the risk of stroke.
Fig. 2: Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.
Fig. 3: Risk of bias summary: review authors’ judgements about each risk of bias item for each included study.
Fig. 4: Pooled odds ratio of high circulating TMAO concentrations for the risk of stroke.
Fig. 5: Mean difference of the circulating TMAO concentrations in stroke versus non-stroke patients.
Fig. 6: Impact of TMAO plasma levels on all-cause mortality.
Fig. 7: Pooled relative risks of high TMAO levels with univariate analysis (UVA) for the risk of major adverse cardiovascular events (MACEs).
Fig. 8: Pooled relative risks of high TMAO levels with multivariate analysis (MVA) for the risk of major adverse cardiovascular events (MACEs).

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All authors contributed to the original and revised manuscript, and due care has been taken to ensure the integrity of the work. HMZ contributed to the manuscript writing and data collection. GFY contributed to manuscript revision and statistical analysis of the data. Both HMZ and GFY contributed to the design of search strategy and criteria for considering studies. In addition, both HMZ and GFY full participated study selection, quality assessment and data extraction.

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Correspondence to Hongmei Zhang.

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Zhang, H., Yao, G. Significant correlation between the gut microbiota-derived metabolite trimethylamine-N-oxide and the risk of stroke: evidence based on 23 observational studies. Eur J Clin Nutr (2022). https://doi.org/10.1038/s41430-022-01104-7

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