Newswise – Cleveland – A new study at the Cleveland Clinic expands the connection between what we eat and how our gut microbiome influences our likelihood of developing various diseases.
Elevated levels of phenylacetylglutamine (PAG), a byproduct produced when microbes in the gut break down dietary proteins, may be directly associated with both the risk and severity of heart failure. Circulation: heart failure. The new findings will enhance researchers’ understanding of how the gut microbiome is linked to heart disease risk through PAG levels, and will help to improve PAG-related risk through interventions such as diet and beta-blocker use. suggests a potential approach to fix the .
Elevated PAG levels were also shown to correspond to types of heart failure. For example, elevated blood PAG was observed in heart failure subjects with preserved ejection fraction. This is a condition in which the heart muscle does not relax enough between beats and becomes too stiff to fill and thus pump blood.
“Measuring PAG levels in blood could offer tremendous value in predicting who is at risk of heart failure,” said Lerner Research Institute’s Director of Cardiovascular and Metabolic Sciences. Stanley Hazen, MD, Ph.D. “This data builds a strong case for increasing the arsenal of heart failure diagnostic tests by making this test accessible to clinicians.”
A team led by Dr. Hazen, who is also co-chair of Preventive Cardiology, previously found links between PAG and cardiovascular disease, including the risk of heart attack, stroke and death, in a 2020 study.. That study showed that PAGs affect the function of adrenergic receptors on platelets, affecting functions such as the risk of blood clotting.
This new study delves deeper into other potential functions of PAG, with a focus on heart failure. Through patient data obtained from thousands of patients in his two independent study cohorts in Europe and the United States, a team of researchers found that PAG levels were associated with heart failure risk. Understand the mechanisms behind the association of PAG with heart failure and the basis for countering its effects.
“This study greatly expands the range of possible associations between our diet and how our gut microbiome acts as a dietary filter, influencing our likelihood of developing various diseases. “In this case, gut microbes form metabolites from the amino acid phenylalanine in food proteins, which adversely affect the function of beating heart muscle cells.”
Targeting PAGs to Resolve Critical Health Conditions
About 6.2 million American adults have heart failure. Heart failure is a condition in which the heart cannot pump enough blood and oxygen to meet the body’s needs. Existing treatments include lifestyle changes such as salt reduction and medications.
“Despite the latest advances in drug and device therapy, heart failure remains one of the leading causes of death and hospitalization in the United States and around the world,” Cardiology, and co-author of the paper. “These studies suggest that a better understanding of how PAG levels can be modified to reduce heart failure risk is worth exploring.”
In the first study on PAG in 2020, Drs. Hazen, Tang and colleagues investigated how PAG affects multiple adrenergic receptors in cells, including beta-adrenergic receptors targeted by beta-blockers. showed. These studies included evidence of using drugs such as carvedilol to counteract the PAG effects.
One of the next steps Dr. Hazen’s team is focusing on is identifying the bacteria and their enzymes that help produce PAGs, and developing treatments to reduce PAGs. Dietary interventions can also help reduce risk, Dr. Hazen says.
Funding for this work has been provided by the National Institutes of Health (NIH) and the Office of Dietary Supplements (P01 HL147823, R01HL103866, R01HL126827) and the Leducq Foundation (17CVD01).
Disclosure: Dr. Hazen, formerly a paid consultant to Procter & Gamble and now a paid consultant to Zena Therapeutics, has a pending Cleveland Clinic holding in connection with cardiovascular diagnostics and treatments. and named co-inventor on issued patents. He also receives research funding from Procter & Gamble, Zehna Therapeutics, and Roche Diagnostics, and Quest Diagnostics, a wholly owned subsidiary of Procter & Gamble, he receives royalty payments from the Cleveland HeartLab for inventions or discoveries related to cardiovascular diagnostics or therapies. I report that I am eligible. and Zehna Therapeutics. Dr. Tang is a consultant to Sequana Medical AG, Owkin Inc, Relypsa Inc, and PreCardiac Inc, has received honoraria from Springer Nature as an author/editor, and has been honored by the American Board for his participation on the study writing committee. It reports that it received compensation from the of Internal Medicine.
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