Gut-brain-heart axis: Metabolite may enable diet and probiotic opportunities

Research has found that bacterial metabolites in the gut may affect the heart through specific brain neurons, revealing a new gut-brain-heart connection. The discovery suggests that increasing these metabolites through diet changes or supplements might help prevent cardiovascular disease. 

Scientists at the Max Delbrück Center detail that the indole-3 acetic acid (IAA) metabolite is key to neuronal activity in the hypothalamus, which controls the relaxation and stiffness of the heart muscle. This metabolite is derived from the essential amino acid tryptophan.

They explain that doctors do not fully understand the reasons behind diastolic dysfunction, where the heart struggles to relax, affecting millions globally.

“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 lead author Bhakti Zakarauskas-Seth, researcher at the Max Delbrück Center, Germany. “It shows that the brain can act as a central hub in gut-heart communication.”

Supplementing fish with IAA

The study in Circulation Research used zebrafish models, which showed that IAA improved heart function. The researchers identified a group of brain neurons called hypocretin (Hcrt) in zebrafish larvae.

Hypothalamus cells produce Hcrt neuropeptides, or orexins, that regulate several involuntary human and fish body functions, such as sleep, eating patterns, and heart activity.

In the study, researchers noticed that when IAA levels fell, Hcrt neurons became overactive, increasing nerve signals to the heart. This process caused the heart muscle to stiffen and not relax properly.

However, when the researchers supplemented the larvae with IAA, neuronal activity normalized, and heart and blood pressure improved. Related hormones such as renin and angiotensinogen were noted to return to healthier levels.

Human relevancy 

Following the fish study, the researchers examined human data from a cohort of patients, which revealed that IAA levels were reduced in patients with hypertension. There was also a sex-specific effect where hypertensive women had significantly lower IAA levels in their serum samples than men.

People with diastolic dysfunction are very common, note the researchers, with up to half of people over 70 having some sort of impairment. The condition is also the underlying mechanism of heart failure, accounting for over 50% of all heart failure cases.

Zakarauskas-Seth believes that for these patients, the study findings open ways for better care: “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.” 

She reflects on a broader message: “The body does not operate in isolated compartments. Gut health, microbial balance, and diet directly shape how well the heart functions.” 

In future studies, researchers will need to validate these findings in other animal models, and clinical studies will need to check whether restoring IAA can help patients.

Heart Health, IAA, Tryptophan, Gut-Brain-Heart Axis, Diastolic Dysfunction, Max Delbrück Center