Gut-Brain-Heart Axis: How Microbes Control Your Blood Pressure

 Will your competent? doctor figure how to use this and stop your blood pressure meds. NO? So, incompetently will DO NOTHING? Won't get human testing going?

Gut-Brain-Heart Axis: How Microbes Control Your Blood Pressure

Sumary: High blood pressure and heart failure might be managed through the gut. New research has identified a direct communication line between gut bacteria, the brain, and the heart. The study reveals that a specific bacterial metabolite called indole-3 acetic acid (IAA) acts as a brake on “stress” neurons in the brain’s hypothalamus.

When IAA levels are low, these neurons become overactive, causing the heart muscle to stiffen—a condition known as diastolic dysfunction. This discovery suggests that diet, probiotics, or IAA supplementation could become powerful new tools for preventing hypertension and heart failure.

Key Facts

• The IAA Brake: Gut microbes produce indole-3 acetic acid (IAA) from the amino acid tryptophan. IAA travels to the brain to regulate hypocretin (Hcrt) neurons.
• Brain as a Hub: Hcrt neurons in the hypothalamus act as the central switch. Without enough IAA, these neurons overfire, sending sympathetic nerve signals that stiffen the heart.
• Diastolic Dysfunction: This research helps explain why the heart struggles to relax in millions of patients—a key driver of heart failure with preserved ejection fraction (HFpEF).
• Human Connection: A study of human patients showed that those with hypertension have lower IAA levels, with a particularly strong effect seen in hypertensive women.
• Biomarker Potential: IAA levels in the blood could serve as an early warning signal for people at high risk of heart failure, allowing for preventative dietary changes.

Source: MDC

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.

Researchers have identified that hypocretin neurons in the brain integrate signals from gut metabolites to regulate the stiffness and relaxation of the heart muscle. Credit: Neuroscience News

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.”

Tracking a signal from gut to brain

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.

Implications for patients and prevention

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.

Key Questions Answered:

Q: How does my gut talk to my heart?

A: It uses the brain as a middleman! Your gut bacteria produce a chemical called IAA from the food you eat. This chemical tells your brain to stay calm. If your gut doesn’t produce enough IAA, your brain gets “stressed” and sends signals that make your heart stiff and your blood pressure rise.

Q: Can I eat my way to a healthier heart?

A: The study suggests that foods rich in tryptophan (like turkey, eggs, and cheese) might help, as gut bacteria turn tryptophan into IAA. However, the key is having the right microbes to do the work. Probiotics or IAA supplements could be the future of heart care.

Q: Why is this especially important for women?

A: The researchers found that hypertensive women had significantly lower levels of IAA than men. This suggests that the gut-brain-heart connection might play a particularly crucial role in cardiovascular health for women.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this neuroscience research news

Author: Gunjan Sinha
Source: MDC
Contact: Gunjan Sinha – MDC
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Indole-3 acetate limits dysbiosis-driven diastolic failure via Hcrt neurons” by Bhakti I. Zakarauskas-Seth, Giovanni Forcari, Harithaa Anandakumar, Ilan Kotlar-Goldaper, Clara Barraud, Nina Jovanovic, Ulrike Brüning, Jennifer Kirwan, Nicola Wilck, Sofia K. Forslund, Dominik N. Müller, Alessandro Filosa, and Suphansa Sawamiphak. Circulation Research
DOI:10.1161/CIRCRESAHA.125.326990

Gut Microbe Secreted Molecule Linked to Formation of New Nerve Cells in Adult Brain

What do I need to eat to generate 5.5 billion neurons in my brain? Why does no one know that answer? 

Gut Microbe Secreted Molecule Linked to Formation of New Nerve Cells in Adult Brain

Summary: Gut microbes that metabolize tryptophan secrete indoles that stimulate the development of new neurons in the adult brain.

Source: Singhealth

The billions of microbes living in your gut could play a key role in supporting the formation of new nerve cells in the adult brain, with the potential to possibly prevent memory loss in old age and help to repair and renew nerve cells after injury, an international research team spanning Singapore, UK, Australia, Canada, US, and Sweden has discovered.

The international investigating team led by Principal Investigator Professor Sven Pettersson, National Neuroscience Institute of Singapore, and Visiting Professor at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore (NTU Singapore), and Sunway University, Malaysia, found that gut microbes that metabolise tryptophan – an essential amino acid – secrete small molecules called indoles, which stimulate the development of new brain cells in adults.

Prof Pettersson and his team also demonstrated that the indole-mediated signals elicit key regulatory factors known to be important for the formation of new adult neurons in the hippocampus, an area of the brain also associated with memory and learning. Memory loss is a common sign of accelerated ageing and often an early sign of the Alzheimer’s disease (AD).

drugs to mimic the action of indoles to stimulate the production of new neurons in the hippocampus or to replace neurons damaged by stroke and spinal injury, as well as designing dietary intervention using food products enriched with indoles as a preventive measure to slow down aging,” said Prof Pettersson.

The international study involved researchers from multiple disciplines and institutions around the world including:

• UK Dementia Research Institute at Imperial College London, UK
• Karolinska Institute, Sweden
• NTU Lee Kong Chian School of Medicine, Singapore
• Murdoch University, Australia
• National Neuroscience Institute, Singapore
• Pennsylvania State University, USA
• University of Toronto, Canada
• Sunway University Malaysia

“The work reported in this paper addresses the formation of neurons in the adult brain. We are currently assessing whether indoles can also stimulate early formation of neurons during brain development. Another area of potential intervention interest is in situations of stroke or spinal injury where there is an urgent need to generate new neurons. It is an interesting and exciting time ahead of us,” said Prof Pettersson.

 

Chemicals from gut bacteria maintain vitality in aging animals

Another case of followup in human testing needed, but won't occur because we have NO strategy.
https://www.mdlinx.com/internal-medicine/medical-news-article/2017/08/23/gut-bacteria-intestinal-bacteria-microbiota-indoles/7372020/?news_id=2386&

Emory's Woodruff Health Sciences Center News

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A class of chemicals made by intestinal bacteria, known as indoles, help worms, flies and mice maintain mobility and resilience for more of their lifespans, scientists have discovered.

The findings were published in PNAS journal on August 21, 2017.

"This is a direct avenue to a drug that could make people live better for longer," said senior author Daniel Kalman, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.

Kalman and his colleagues use the term "healthspan" to describe the length of time a human or animal, while aging, can stay active and resist stress. In this research, the focus is on whether the animals live healthier, but not necessarily longer.

Indole, produced by many types of bacteria through breakdown of the amino acid tryptophan, can smell noxious or flowery depending on the concentration. Indole and its chemical relatives can be found in plants, especially vegetables such as broccoli and kale. One such relative is also known as auxin, a growth hormone for plants needed for light–seeking and root development.

Kalman's lab had previously identified indole and related molecules as compounds released by E. coli bacteria that condition the worm C. elegans and mice to be more resistant to infection and other stresses.

Worms normally eat bacteria. So researchers fed them E. coli bacteria that produce indoles, and compared them with worms fed E. coli that cannot produce indoles.

As they age, older worms spend less time moving around, can't swallow as well and are more sensitive to stressors. Although indoles didn't change the maximal lifespan, they markedly increased the amount of time worms were mobile after the age of 15 days, and it increased their swallowing strength and resistance to heat stress, even in young animals.

In addition, worms usually stop reproduction at the age of 5 days, but dietary indole more than doubled their reproductive span, allowing them to remain fertile up to 12 days.

Indole had similar effects on mobility and resistance to heat in Drosophila fruit flies, and with mice, a comparable pattern was evident. Researchers treated mice with antibiotics to eliminate the existing flora, and then re–colonized them with either normal E. coli, or, as a control, with bacteria that cannot produce indole. In very old mice (28 months), indoles helped animals maintain their weight, mobility and activity levels. In younger mice, indoles extended survival after exposure to lethal radiation.

The researchers also analyzed the patterns of gene activity affected by indoles – the genes regulated by indoles were distinct from other C. elegans genes previously linked to longevity.

Indoles may be keeping the intestinal barrier intact and/or limiting systemic inflammatory effects. Kalman's laboratory is now investigating how indoles exert their effects in aging animals, how dysregulation of indoles produced by the microbiota contribute to frailty, and how indoles can be used to reverse these effects.

"Indole is such an ancient messenger," Kalman said. "It's how plants steer their growth, how bacteria talk to each other, and it is how plants and bacteria talk with us and ensure proper homeostasis with our immune system. It is perhaps not so surprising that these molecules help maintain our vitality."

The first author of the paper is postdoctoral fellow Robert Sonowal, PhD. Co–authors include professor of pathology Guy Benian, PhD, assistant professor of pediatrics Rheinallt Jones, PhD, and professor of geriatrics Jonathan Flacker, MD.