Significant correlation between the gut microbiota-derived metabolite trimethylamine-N-oxide and the risk of stroke: evidence based on 23 observational studies.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 35468932 · doi:10.1038/s41430-022-01104-7
What was done
Authors conducted a systematic review and meta-analysis of observational studies published between January 1, 2001, and June 1, 2021, searching PubMed, Embase, Cochrane Library, and Web of Science. They pooled data from 23 studies involving 30,808 participants to evaluate the association between circulating trimethylamine-N-oxide (TMAO) concentrations and the risk of stroke, major adverse cardiovascular events (MACEs), and all-cause mortality.
What was found
Individuals in the higher TMAO category had significantly higher odds of stroke (OR 1.83, 95% CI 1.02–3.29, P = 0.04). Stroke patients had higher mean circulating TMAO concentrations than non-stroke controls (mean difference 2.20 µmol/L, 95% CI 1.23–3.16, P < 0.00001). Higher TMAO levels were associated with increased all-cause mortality (HR 1.89, 95% CI 1.15–3.08, P = 0.01) and MACEs in both univariate analysis (RR 2.26, 95% CI 2.01–2.54, P < 0.00001) and multivariate analysis (RR 1.55, 95% CI 1.17–2.05, P = 0.002).
Why it matters
This meta-analysis aggregates human observational data indicating that elevated levels of the gut microbiota-derived metabolite TMAO correlate with cerebrovascular risk and vascular mortality.
Limits
All included studies were observational, which prevents causal inference. The abstract does not report study heterogeneity, dietary controls, renal function adjustments, or distinctions between stroke subtypes.