Cleveland Clinic study links gut microbiome to aggressive prostate cancer

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October 28, 2021, CLEVELAND: Cleveland Clinic researchers have shown for the first time that gut molecules associated with diet are associated with aggressive prostate cancer, suggesting that dietary interventions may help reduce risk. The results of the study were published in Cancer epidemiology, biomarkers and prevention.

Although more research is needed, the lead author of the study Nima Sharifi, MD., says the results of the team’s analysis of nearly 700 patients may have clinical implications for the diagnosis and prevention of fatal prostate cancer.

“We have found that men with higher levels of certain diet-related molecules are more likely to develop aggressive prostate cancer,” said Dr. Sharifi, director of the Cleveland Clinic. Genitourinary Malignancies Research Center. “As we continue our research in this area, our hope is that one day these molecules can be used as early biomarkers of prostate cancer and help identify patients who may modify their risk of disease by changing their diet and diet. way of life. ”

In this study, Dr. Sharifi and his collaborators, including Stanley Hazen, MD, Ph.D.., and Eric Klein, MD. – analyzed data from patients previously enrolled in the National Cancer Institute’s Prostate, Lung, Colon and Ovarian Cancer (PLCO) screening trial.

They studied the baseline levels of certain dietary nutrients and metabolites (byproducts produced when a substance is broken down in the gut) found in the blood serum of patients before prostate cancer was diagnosed. They compared serum levels between healthy patients and those who were later diagnosed with prostate cancer and died of the disease.

Researchers found that men with high levels of a metabolite called phenylacetylglutamine (PAGln) were about two or three times more likely to be diagnosed with fatal prostate cancer. This metabolite is produced when microbes in the gut break down phenylalanine, an amino acid found in many plant and animal protein sources such as meat, beans, and soybeans.

In addition to PAGln, researchers also found that high levels of two nutrients abundant in animal products, including red meat, egg yolks, and high-fat dairy products called choline and betaine, were also linked to an increased risk of aggressive prostate cancer.

While these gut nutrients and metabolites have previously been studied in heart disease and stroke, this is the first time that gut microbiome metabolites have been clinically studied in relation to prostate cancer outcomes.

Dr Hazen was the first to identify the association of PAGln with an increased risk of cardiovascular disease. The results were published in 2020 in Cell. “Interestingly, we found that PAGln binds to the same receptors as beta blockers, which are drugs commonly prescribed to help lower blood pressure and the risk of subsequent cardiac events,” said the Dr Hazen, Director of the Cleveland Clinic. Center for Microbiome and Human Health and president of the Lerner Research Institute Department of Cardiovascular and Metabolic Sciences. “This suggests that part of the potent efficacy of beta blockers may be due to blocking the activity of the metabolite.”

“New information is emerging from large-scale clinical data sets that show beta blocker use is also associated with lower prostate cancer mortality,” said Dr Sharifi, who is a breast physician. from the Lerner Research Institute. Department of Cancer Biology. “We will continue to work together to study possible mechanisms linking PAGln activity and prostate cancer disease processes in the hope of identifying new therapeutic targets for our patients.”

The research team will also continue to explore the reliability of the use of choline, betaine and PAGln as biomarkers of aggressive prostate cancer and how dietary interventions can be used to modulate their levels and reduce the risk of prostate cancer. subsequent illness of patients.

Chad Reichard, MD, urologist oncologist at Urology of Indiana and former urology resident at the Cleveland Clinic, and Bryan Naelitz, a medical student in Dr. Sharifi’s lab, are the co-first authors of the study. Dr Klein is a urologist and Chairman Emeritus of the Glickman Urological & Kidney Institute at the Cleveland Clinic. The research was supported by the National Cancer Institute and the National Heart, Lung, and Blood Institute (both part of the National Institutes of Health), as well as the Prostate Cancer Foundation.

About the Cleveland Clinic

Cleveland Clinic – now in its centenary – is a non-profit, multi-specialist academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision to provide exceptional patient care based on the principles of cooperation, compassion and innovation. The Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass grafting and the first face transplant in the United States. American News and World Report regularly names the Cleveland Clinic as one of the best hospitals in the country in its annual “America’s Best Hospitals” survey. Among the 70,800 Cleveland Clinic employees worldwide, there are more than 4,660 salaried physicians and researchers, and 18,500 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. The Cleveland Clinic is a 6,500-bed healthcare system that includes a 173-acre main campus near downtown Cleveland, 19 hospitals, more than 220 outpatient facilities and locations in Southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, United Arab Emirates; and London, England. In 2020, there were 8.7 million total outpatient visits, 273,000 hospital admissions and observations, and 217,000 surgical cases across the Cleveland Clinic healthcare system. Patients came for treatment from all states and 185 countries. Visit us at clevelandclinic.org. follow us on twitter.com/ClevelandClinic. News and resources available on pressroom.clevelandclinic.org.



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