A new review suggests that the aftermath of a heart attack may rely in part on signals from the gut and reveals how microbial metabolites influence inflammation, scarring and recovery through epigenetic mechanisms.
Research: Gut-heart dialogue: An epigenetic perspective on myocardial infarction. Image credit: Joyisjoyful / Shutterstock
In a recent review published in a magazine npj biofilm and microbiomeOur group reviewed the evidence on how metabolites from the gut microbiota influence myocardial infarction (MI) through epigenetic mechanisms and identified potential therapeutic avenues.
background
Each year, millions of people experience myocardial infarction (commonly known as a heart attack), but recovery outcomes vary widely. Why do some hearts heal better than others?
Several studies show increasing evidence for new factors in cardiovascular disease risk. The gut microbiome may be a hidden culprit, making it an area of interest for researchers studying heart health.
Microbial metabolites produced in the intestine, such as short-chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO), can influence inflammatory and metabolic processes in the body. Factors such as deoxyribonucleic acid (DNA) methylation and histone modifications also control how genes work without changing the DNA sequence.
Together, these create regulatory axes that influence cardiac outcomes, but further research is needed to translate these insights into clinical treatment.
connection between the intestines and the heart
The gut microbiome supports digestion, immune function, and metabolic balance. When healthy, the microbes in your gut produce SCFAs that help reduce inflammation, protect the intestinal lining, and prevent your body from making too much fat. However, people who have had a heart attack have an imbalanced gut (dysbiosis) that results in lower levels of SCFAs but higher levels of production of other substances that can be harmful to the body, such as TMAO and lipopolysaccharides. An imbalance between SCFA, TMAO, and lipopolysaccharide leads to increased inflammation and increased cardiac damage.
Microbiota changes with each disease stage
The role of the gut microbiota in MI evolves across different stages of the disease. Before a heart attack, microbial imbalances are associated with atherosclerosis (plaque buildup in the arteries), where reduced levels of butyrate-producing bacteria weaken plaque stability and metabolites such as TMAO increase the risk of blood clot formation.
A heart attack causes severe stress and causes leaky gut, which allows toxins to enter the bloodstream and cause inflammation. Studies reviewed by the authors show that harmful bacterial species increase while beneficial microorganisms decrease, further worsening heart damage.
Persistent dysbiosis can cause permanent detrimental changes in heart structure. This unhealthy condition can lead to fibrosis and progress to heart failure. However, preclinical studies have shown that restoring good bacteria may improve heart function and reduce damage, demonstrating the need for a balanced gut during recovery.
Epigenetics: molecular cross-linking
The relationship between dysbiosis and heart disease is epigenetics. Epigenetics refers to changing gene expression without changing the actual DNA sequence. This is achieved through processes such as DNA methylation, histone modifications, and regulatory non-coding ribonucleic acids (RNAs).
DNA methylation and gene regulation
DNA methylation involves adding chemical groups to DNA that can turn genes on and off. During MI, aberrant methylation patterns activate inflammatory genes while suppressing protective genes. Harmful metabolites, such as TMAO, can increase DNA methylation and reduce the activity of genes that protect the heart. In contrast, beneficial microbial metabolites help maintain balanced gene expression, support recovery, and reduce damage.
Histone modification and inflammation
Histones are proteins that package DNA, and their arrangement changes the way the DNA wraps, making some genes more or less available. SCFAs act as natural histone deacetylase inhibitors and, by loosening chromatin structure, can reduce inflammation and promote expression of genes that promote protective responses (e.g., reduce scar tissue in the heart, reduce cell loss after a heart attack, and improve cardiac recovery). Other microbial metabolites also modulate advanced histone modifications, further supporting cardiac function and recovery.
non-coding RNA
Noncoding RNAs, such as microRNAs, long noncoding RNAs, and circular RNAs, control gene expression at the posttranscriptional level. Gut-derived signals influence these molecules, shaping inflammation, fibrosis, and cell survival.
For example, lipopolysaccharides can activate pro-inflammatory microRNAs and worsen cardiac damage. In contrast, beneficial metabolites suppress harmful pathways and increase the expression of defense genes. This hierarchical control allows the gut microbiota to fine-tune the cardiac response to stress and injury.
Implications for treatment: from diet to drugs
Understanding how the gut microbiome influences our genes can lead to new treatments. Diet is an important way to balance the intestinal flora. A high-fiber diet increases SCFA production, reduces inflammation, and supports heart health. Foods such as fruits, vegetables, and nuts produce compounds that improve gene regulation and mitochondrial function. Dietary patterns such as intermittent fasting and caloric restriction may further enhance beneficial epigenetic modifications, thereby promoting recovery after MI.
Drugs that mimic microbial metabolites are also therapeutic targets among several drug modalities under development. By acting as histone deacetylase inhibitors, these drugs may produce anti-inflammatory effects through the same mechanism by which SCFAs exert their cardioprotective effects via histone acetylation, thus improving cardiac function.
Probiotics and fecal microbiota transplants are the latest treatments being studied to address dysbiosis, and these methods may reduce inflammation, improve heart health, and reverse dysbiosis. Postbiotics also have the potential to be a safe and controlled alternative for restoring a healthy microbiome, but their clinical use is hampered by a number of challenges, including variable patient response, safety concerns, and limited clinical evidence supporting efficacy.
conclusion
This review suggests that MI is not just a cardiovascular event, but a systemic condition influenced by the gut microbiota and epigenetic regulation. Gut microbiota and epigenetics influence inflammation, cardiac repair, and long-term outcomes. Lifestyle factors such as diet have been shown to be important in determining overall heart health. New therapies targeting the gut microbiome and genes may offer future benefits in both the prevention and treatment of heart disease. However, before these treatments can be widely used, individual differences in people and clinical safety need to be resolved.
Reference magazines:
- Song, J., Tang, S., Guo, Y., Hong, C., and Song, T. (2026). Dialogue between the gut and the mind: An epigenetic perspective on myocardial infarction. npj biofilm and microbiome. DOI: 10.1038/s41522-026-00974-0, Nature, https://www.nature.com/articles/s41522-026-00974-0
