Millions of people worldwide suffer from high blood pressure or heart failure. In many cases, the cause is diastolic dysfunction – caused by an increasingly stiff heart muscle that finds it difficult to relax and fill completely with blood. Why the heart stiffens is not yet fully understood.
A team led by Dr Suphansa Sawamiphak, head of the Cardiovascular-Haematopoietic Interaction working group at the Max Delbrück Centre, has now discovered that gut bacteria could play a crucial role in this disease process. In experiments using zebrafish as a model, the researchers discovered that certain microbes in the gut produce a small molecule called indole-3-acetic acid (IAA) from the amino acid tryptophan. IES acts on neurons in the brain, which in turn control the heart. Sawamiphak and her colleagues present this direct link between bacteria, the brain and the heart in the journal Circulation Research.
"We were surprised that a single bacterial metabolite could simultaneously affect the central nervous system, the heart and important hormone systems," says the study's lead author, Bhakti Zakarauskas-Seth from Sawamipha's team. "This shows that the brain can act as a central hub in the communication between the gut and the heart."
High blood pressure caused by overactive neurons
To understand how gut bacteria could affect the heart, the researchers focused on a group of neurons in the hypothalamus of zebrafish larvae that produce specific neuropeptides called hypocretins (Hcrt). These messenger substances, also known as orexins, regulate many involuntary functions in the body, such as sleep and hunger, but also heart activity. When the IES levels dropped in the zebrafish larvae, the Hcrt neurons became overactive. This amplified their sympathetic nerve signals to the heart, causing the heart muscle to stiffen and reducing its ability to relax completely.
When the scientists administered IES to the larvae, neural activity normalised. Heart function and blood pressure improved, and even related hormones such as renin and angiotensinogen returned to healthier levels.
In the next step, Zakarauskas-Seth and colleagues examined data from a group of patients. Humans also possess Hcrt neurons. The researchers found that IES values were reduced in patients with hypertension. Notably, they observed a sex-specific effect: women with hypertension exhibited significantly lower IES values in their serum samples compared to men suffering from the condition.
For Prevention and Therapy
Diastolic dysfunction is highly prevalent—almost half of all individuals over 70 years of age exhibit at least mild symptoms. It is the underlying cause of heart failure with preserved ejection fraction (HFpEF), which affects more than 50 percent of patients with heart failure.
For these individuals, the findings of their work open several possibilities, says Zakarauskas-Seth: “IES levels could serve as a biomarker to identify patients at high risk for hypertension or heart failure. Therapeutically, increasing IES concentrations—through diet, probiotics, or nutritional supplements—could represent a novel strategy for preventing or treating cardiovascular disease.”
The fact that a single bacterial metabolite can influence the central nervous system, the heart, and the endocrine system is an important message, adds Zakarauskas-Seth. “The body does not operate in isolated compartments: gut health, microbial balance, and nutrition directly affect how well the heart functions.” The researchers now plan to validate their findings in other animal models. To determine the actual benefit that patients might derive from elevated IES levels, clinical studies will also be required.
Further Informationen:
Working Group on Cardiovascular-Haematopoietic Interaction
Heart repair via neuroimmune crosstalk
Original publication: Bhakti I. Zakarauskas-Seth, Giovanni Forcari, Harithaa Anandakumar et al., Indole-3 Acetate Limits Dysbiosis-Driven Diastolic Failure via Hcrt Neurons, Circulation Research, February 2026.
Scientific Contact:
Dr. Suphansa Sawamiphak
Head of the Cardiovascular-Haematopoietic Interaction Working Group
Max Delbrück Centre
Suphansa.Sawamiphak(at)mdc-berlin.de
Source: Press release Max Delbrück Centre
