Gut microbiota metabolites and risk of major adverse cardiovascular events and death: A systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of prospective observational cohort studies
PubMed 39259062 · doi:10.1097/MD.0000000000037825
What was done
Systematic review and random-effects meta-analysis of prospective observational studies identified via MEDLINE and Scopus through August 2023. The authors evaluated associations of circulating gut microbial metabolites (TMAO, betaine, L-carnitine, and choline) with major adverse cardiovascular events (MACE) and all-cause mortality, pooling unadjusted or multivariable-adjusted hazard ratios from 30 prospective cohort studies comprising 48,968 participants.
What was found
Elevated TMAO concentrations were associated with an increased risk of MACE (HR: 1.41, 95% CI 1.20 to 1.54, P < .00001, I2 = 43%) and all-cause mortality (HR: 1.55, 95% CI 1.37 to 1.75, P < .00001, I2 = 46%) compared to low TMAO levels. High levels of L-carnitine and choline were also significantly associated with increased risk of MACE, whereas betaine showed no significant difference for MACE. Numerical risk estimates and confidence intervals for precursors were not reported in the abstract.
Why it matters
This review pools large-scale prospective cohort data linking elevated TMAO and select precursor metabolites to increased cardiovascular events and death, supporting the role of gut microbial metabolic pathways as potential prognostic markers.
Limits
All included studies were observational cohorts, meaning residual confounding cannot be ruled out and causality cannot be established. The abstract does not provide numerical effect estimates or confidence intervals for L-carnitine, choline, or betaine, nor does it specify the cutoffs used across studies to define high versus low metabolite concentrations.
Cited by
- supports High circulating levels of TMAO over time carry cardiovascular risk.