The Gut-Heart Axis: Molecular Perspectives and Implications for Myocardial Infarction

Abstract

Myocardial infarction (MI) remains the leading cause of death globally, imposing a significant burden on healthcare systems and patients. The gut-heart axis, a bidirectional network connecting gut health to cardiovascular outcomes, has recently emerged as a critical factor in MI pathophysiology. Disruptions in this axis, including gut dysbiosis and compromised intestinal barrier integrity, lead to systemic inflammation driven by gut-derived metabolites like lipopolysaccharides (LPSs) and trimethylamine N-oxide (TMAO), both of which exacerbate MI progression. In contrast, metabolites such as short-chain fatty acids (SCFAs) from a balanced microbiota exhibit protective effects against cardiac damage. This review examines the molecular mediators of the gut-heart axis, considering the role of factors like sex-specific hormones, aging, diet, physical activity, and alcohol consumption on gut health and MI outcomes. Additionally, we highlight therapeutic approaches, including dietary interventions, personalized probiotics, and exercise regimens. Addressing the gut-heart axis holds promise for reducing MI risk and improving recovery, positioning it as a novel target in cardiovascular therapy.

Keywords: gut metabolites; gut microbiota; gut–heart axis; intestinal barrier; myocardial infarction.

Figure 1

Host–microorganism interface. (A) Schematic representation of the main components of the intestinal barrier. (B) Junctional complexes linking adjacent epithelial cells in normal and impaired intestinal barrier.

Figure 2

Complexity of the gut microbiota and its adaptation to different microenvironments in the lower GI tract. Four major bacterial phyla (Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria) are found in different sections of the GI tract. Oxygen levels decrease progressively from the stomach to the colon, reflecting a shift from an aerobic to an anaerobic environment. Population density and mucus thickness both increase from the stomach to the colon, corresponding with higher microbial diversity and density in the large intestine, while pH decreases along the tract, providing favorable conditions for specific bacterial communities in different regions.

Figure 3

Risk factors in the gut–heart axis in health and disease. In a healthy state (eubiosis), factors like exercise and a fiber- and antioxidant-rich diets support beneficial gut bacteria, boosting SCFA production and limiting harmful compounds like TMA and LPS. Conversely, risk factors such as a Western diet, aging, antibiotics, and pollution lead to gut dysbiosis, where pathogenic bacteria increase inflammatory mediators, impair gut integrity, and raise systemic inflammation and MI risk.