Key result
Specific gut microbiota link to major CHD events, potentially mediated by immune cell traits.
Why the study?
Gut microbiota and immune cells are increasingly recognized to be associated with MACE, but the precise mechanisms remain unclear.
Do genetically predicted gut microbiota and immune cell traits affect the risk of major coronary heart disease events?
Observational
Do genetically predicted gut microbiota and immune cell traits affect the risk of major coronary heart disease events?
This study provides genetic evidence linking specific gut microbiota and immune cell traits to major coronary heart disease events, highlighting potential immune-mediated pathways for future therapeutic targeting.
Supports potential immune-mediated gut microbiota effects on CHD; hypothesis-generating and requires prospective validation before practice change.
As one of the primary composite endpoints in cardiovascular clinical research, major adverse cardiac events (MACE) are associated with poor clinical outcomes in patients with cardiovascular diseases. Gut microbiota and immune cells are increasingly recognized to be associated with MACE. However, the precise mechanisms remain unclear. We retrospectively analyzed the global burden of ischemic heart disease (IHD) and ischemic stroke (IS), 2 major contributors to the overall burden of MACE, by extracting data from the Global Burden of Disease database, and two-sample Mendelian randomization (MR) using the FinnGen R9 I9_CHD dataset as the outcome to investigate the genetically predicted associations between gut microbiota, immune cell traits, and major coronary heart disease events. In 2021, global IHD prevalence reached 254.3 million cases, a 1.4% increase from 1990, whereas IS prevalence declined by 39.6% over the same period. Results of Mendelian randomization analysis provided evidence supporting genetically predicted associations between 21 gut microbiota, 31 immune cells, and major coronary heart disease event. Sensitivity tests confirmed our findings. Additionally, mediation analysis suggested that the association between gut microbiota and major coronary heart disease event may be partly mediated through immune cell traits. Our study provides both an updated epidemiological profile of IHD/IS and genetic evidence linking gut microbiota and immune cell traits to coronary events, with immune cells potentially acting as mediators. These findings provide a foundation for future mechanistic studies and may facilitate the identification of candidate therapeutic targets, although further experimental validation is required.
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Liu et al. (2026) conducted an observational in Major adverse cardiac events (MACE), ischemic heart disease (IHD), ischemic stroke (IS). Genetically predicted gut microbiota and immune cell traits was evaluated on Major coronary heart disease event. Mendelian randomization analysis identified genetically predicted associations between 21 gut microbiota, 31 immune cells, and major coronary heart disease events, with immune cells potentially acting as mediators.
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