Gut butyrate-producers confer post-infarction cardiac protection

Area of Science:

• Microbiology
• Cardiology
• Metabolomics

Background:

• The gut microbiome's influence on cardiovascular diseases is recognized, but its specific role in myocardial infarction (MI) injury is unclear.
• Investigating the gut microbiome's impact on cardiac response post-MI is crucial for understanding disease mechanisms.

Purpose of the Study:

• To determine the role of gut microbial metabolites in the human myocardial infarction (MI) injury response.
• To identify specific gut bacteria and their metabolites that influence cardiac function after MI.

Main Methods:

• 16S V3-V4 next-generation sequencing, metagenomics, and machine learning on stool samples from ST-elevation MI (STEMI) patients.
• Validation in a nonhuman primate ischemia/reperfusion model.
• Gnotobiotic and HMGCS2-deficient mouse models to assess the functional impact of specific bacteria and beta-hydroxybutyrate.

Main Results:

• An enrichment of butyrate-producing bacteria was identified in STEMI patients.
• Inoculation with these bacteria in mice led to beta-hydroxybutyrate production, supporting cardiac function post-MI.
• HMGCS2-deficient mice, lacking endogenous ketogenesis, showed improved cardiac function post-MI upon bacterial inoculation, with increased plasma ketone levels.

Conclusions:

• Gut butyrate-producing bacteria play a previously unrecognized protective role in the post-myocardial infarction response.
• Bacterial-derived beta-hydroxybutyrate supports cardiac function and improves outcomes following MI.
• Targeting the gut microbiome may offer novel therapeutic strategies for managing myocardial infarction.