Researchers at the Max Delbrück Center uncover how a bacterial metabolite produced in the gut regulates heart function through specific brain cells. The findings, published in Circulation Research , reveal a new gut-brain-heart axis and point to potential therapies for hypertension and heart failure.
Hypertension and heart failure affect millions worldwide. Yet in many patients, doctors cannot fully explain why the heart becomes stiff and struggles to relax – a condition known as diastolic dysfunction.
Researchers in the lab of Dr. Suphansa Sawamiphak, Group Leader of Cardiovascular-Hematopoietic Interaction at the Max Delbrück Center, have identified a direct communication line between gut bacteria, the brain, and the heart. Using zebrafish as a model, the team discovered that certain gut microbes produce a small molecule called indole-3 acetic acid (IAA) from the dietary amino acid tryptophan. IAA acts on neurons in the brain, which in turn, control the heart. The study was published in “Circulation Research.”
“We were surprised that a single bacterial metabolite could influence the central nervous system, the heart, and major hormonal systems at the same time,” says Bhakti Zakarauskas-Seth, lead author of the paper. “It shows that the brain can act as a central hub in gut-heart communication.”
To understand how gut bacteria might influence the heart, the researchers focused on a distinct group of neurons in the hypothalamus known as hypocretin (Hcrt) in zebrafish larvae. These cells produce Hcrt neuropeptides, also known as orexins, regulate many involuntary functions in the body, such as sleep and eating patterns, but also heart activity. When IAA levels dropped, Hcrt neurons became overactive. This increased sympathetic nerve signals to the heart, causing the heart muscle to stiffen, impairing its ability to relax properly.
When the researchers supplemented the larvae with IAA, neuronal activity normalized, heart function and blood pressure improved, and even related hormones such as renin and angiotensinogen returned to healthier levels.
They then examined data from a cohort of patients – humans also have Hcrt neurons – and found that IAA levels were reduced in patients with hypertension. Notably, they observed a sex-specific effect, with hypertensive women showing significantly lower levels of IAA in their serum samples than men.
Diastolic dysfunction very common – up to half of all people over age 70 have some level of impairment. It is also is the underlying functional mechanism of heart failure with preserved ejection fraction (HFpEF), which accounts for over 50% of all heart failure cases.
For these patients, the findings open several potential avenues for better care, says Zakarauskas-Seth. “IAA levels could serve as a biomarker to identify patients at high risk of hypertension or heart failure. Therapeutically, boosting IAA production – for example through diet, probiotics, or supplementation – could become a new strategy to prevent or treat cardiovascular disease.”
That a single bacterial metabolite can influence the central nervous system, the heart, and major hormonal system also underscores a broader message, she adds. “The body does not operate in isolated compartments. Gut health, microbial balance, and diet directly shape how well the heart functions.” The researchers will need to validate their findings in other animal models and clinical studies will be needed to determine whether restoring IAA can benefit patients.
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association lays the foundation for the medicine of tomorrow through our discoveries of today. At locations in Berlin-Buch, Berlin-Mitte, Heidelberg, and Mannheim, interdisciplinary teams investigate the complexity of disease at the systems level – from molecules and cells to organs and entire organisms. Together with academic, clinical, and industry partners, and as part of global networks, we turn biological insights into innovations for early detection, personalized therapies, and disease prevention. Founded in 1992, the Max Delbrück Center is home to a vibrant, international research community of around 1,800 people from over 70 countries. We are 90 percent funded by the German federal government and 10 percent by the state of Berlin.
Circulation Research
Experimental study
Cells
Indole-3 acetate limits dysbiosis-driven diastolic failure via Hcrt neurons
19-Feb-2026