Nima Sharifi, MD, Director, Center for GU Malignancies Research at the Cleveland Clinic speaks about Gut Microbiome-Dependent Metabolic Pathways and Risk of Lethal Prostate Cancer: Prospective Analysis of a PLCO Cancer Screening Trial Cohort.
Link to Article:
https://newsroom.clevelandclinic.org/2021/10/28/cleveland-clinic-study-links-gut-microbiome-and-aggressive-prostate-cancer/
For the first time, Cleveland Clinic researchers have discovered that diet-related chemicals in the stomach are linked to aggressive prostate cancer, implying that dietary changes could help reduce risk. The study’s findings were published in the journal Cancer Epidemiology, Biomarkers & Prevention.
While further research is needed, lead author Nima Sharifi, M.D., believes the findings from the team’s review of over 700 individuals could have therapeutic implications for diagnosing and preventing fatal prostate cancer.
Dr. Sharifi and his colleagues evaluated data from individuals previously enrolled in the National Cancer Institute’s Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which included Stanley Hazen, M.D., Ph.D., and Eric Klein, M.D.
Prior to prostate cancer diagnosis, researchers looked at baseline levels of key dietary components and metabolites (byproducts formed when a substance is broken down in the gut) identified in patients’ blood serum. They compared serum levels in healthy patients to those who were later diagnosed with prostate cancer and died from it.
Men with high levels of a metabolite termed phenylacetylglutamine (PAGln) were two to three times more likely to be diagnosed with fatal prostate cancer, according to the study. When microorganisms in the gut break down phenylalanine, an amino acid found in many plant- and animal-based protein sources like meat, beans, and soy, this metabolite is generated.
In addition to PAGln, researchers revealed that high levels of choline and betaine, two nutrients found in animal sources such as red meat, egg yolks, and high-fat dairy products, were connected to an increased risk of aggressive prostate cancer.
While these nutrients and gut metabolites have previously been investigated in the context of heart disease and stroke, this is the first clinical study of gut microbiome metabolites in connection to prostate cancer outcomes.
Dr. Hazen was the first to link PAGln to a higher risk of cardiovascular disease. The findings were published in the journal Cell in 2020. Dr. Hazen, director of Cleveland Clinic’s Center for Microbiome & Human Health and chair of Lerner Research Institute’s Department of Cardiovascular & Metabolic Sciences, said, “Intriguingly, we found that PAGln binds to the same receptors as beta blockers, which are drugs commonly prescribed to help lower blood pressure and thus the risk of cardiac events.”
The researchers will also look at the validity of employing choline, betaine, and PAGln as biomarkers for aggressive prostate cancer, as well as how dietary interventions might be utilized to modulate their levels and lower patients’ disease risk.
The study’s co-first authors are Chad Reichard, M.D., a urologic oncologist at Urology of Indiana and a former urology trainee at Cleveland Clinic, and Bryan Naelitz, a medical student in Dr. Sharifi’s lab who is currently a urology resident. Dr. Klein is a urologist and the emeritus chair of Cleveland Clinic’s Glickman Urological & Kidney Institute. The research was funded by the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the Prostate Cancer Foundation, all of which are part of the National Institutes of Health.