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A new study from Lawson Health Research Institute and Western University illustrates how the gut microbiome interacts with an oral medication in prostate cancer patients, suggesting bacteria in the gut play a role in treatment outcomes. The findings, published in Nature Communications, highlight how the drug abiraterone acetate is metabolized by bacteria in the gut to reduce harmful organisms while promoting those that fight cancer. The team suspects this is one of many examples of how the microbiome influences our response to medications. 

“Research is beginning to uncover the ways in which the human microbiome influences cancer development, progression and treatment,” explains Brendan Daisley, a PhD candidate at Western’s Schulich School of Medicine & Dentistry who is conducting research at Lawson. “Our study highlights a key interaction between a cancer drug and the gut microbiome that results in beneficial organisms with anti-cancer properties.”

Traditional prostate cancer therapies are designed to deprive the body of hormones called androgens, which are responsible for prostate cancer growth. 

“Unfortunately, traditional androgen deprivation therapies are not always effective,” explains Dr. Joseph Chin, Lawson Associate Scientist, Professor at Schulich Medicine & Dentistry and Urologist at London Health Sciences Centre (LHSC). "In those cases, alternative therapies are explored.”

Abiraterone acetate is a highly effective therapy used in the treatment of prostate cancer that has been resistant to other treatments. While abiraterone acetate also works to reduce androgens in the body, it does so through a different mechanism and, unlike traditional therapies, it is taken orally. 

“When drugs are taken orally, they make their way through the intestinal tract where they come into contact with billions of microorganisms,” says Dr. Jeremy Burton, Lawson Scientist, Associate Professor at Schulich Medicine & Dentistry and lead researcher on the study. “While it’s long been a mystery why abiraterone acetate is so effective, our team wondered if the gut microbiome plays a role.”

The team’s study included 68 prostate cancer patients from LHSC, including those being treated with abiraterone acetate and those being treated with traditional androgen deprivation therapies. The research team collected and analyzed patient stool samples, and conducted further experiments in their laboratory at St. Joseph’s Health Care London.

They discovered that patients’ gut microbiomes changed drastically after taking abiraterone acetate. Bacteria in the gut metabolized the drug leading to a significant increase in a bacterium called Akkermansia muciniphila. Referred to as a ‘next-generation probiotic,’ this bacterium’s relevance has recently been explored in several large cancer studies. It’s been shown to facilitate a better response to cancer immunotherapy drugs and it can elicit a wide range of other positive health benefits as well. The increase in Akkermansia muciniphila also led to an increased production of vitamin K2 which is known for anti-cancer properties that can inhibit tumour growth. 

The team also observed the impact of androgen depletion on the microbiome. Both abiraterone acetate and traditional androgen deprivation therapies led to a decrease in organisms that utilize androgen. 

“These findings clearly demonstrate that the gut microbiome is playing a role in treatment response,” notes Dr. Burton.

The team hopes to further explore drug-microbiome interactions with a goal of harnessing the microbiome to improve treatment outcomes for a variety of diseases. In another study, they are exploring whether fecal microbiota transplants from a healthy donor can change the microbiome of melanoma patients to increase organisms like Akkermansia muciniphila and improve response to immunotherapy. They also plan to study whether analysis of a patient’s microbiome can be used to predict their response to specific therapies.

“While more research is needed, we may one day be able to analyze a patient’s microbiome to determine the best course of treatment or even influence the microbiome to improve outcomes,” says Dr. Burton. “This could lead to a new frontier in personalized medicine.”

The study was made possible through the generous support of The W. Garfield Weston Foundation, St. Joseph’s Health Care Foundation and the Canadian Urologic Oncology Group. 

Lawson Health Research Institute was awarded over $1.2 million in the Canadian Institutes of Health Research’s Fall 2019 Project Grant competition, for three projects including one Priority Announcement. 

“This is a great accomplishment for the successful researchers at Lawson and those working across the city,” says Dr. David Hill, Lawson Scientific Director. “At Lawson, our scientists target rapid response research that can be quickly incorporated into improved care for patients and families. Our research happens within hospital walls, where care is delivered, with innovations that improve lives every day.” 

Western University received more than $11.9 million in research funding through the project grant competition for 17 projects. A special congratulation to Lawson researchers Drs. Samuel Asfaha, Thomas Appleton, Neil Duggal, David Spence and Zhu-Xu Zhang, as well as Dr. Subrata Chakrabarti, recipient of the CIHR Priority Announcement for “Novel mechanisms in diabetic cardiomyopathy.”

Selective Brain Hypothermia via Intranasal Cooling to Limit Brain Injury Post Cardiac Arrest
Dr. Ting-Yim Lee 

There are 40,000 cardiac arrests per year in Canada. Within the body, it triggers a complex cascade of dysfunction resulting in cell death, even after successful cardiopulmonary resuscitation, with only three to seven per cent of survivors returning to normal function. 

To reduce the high incidence of brain damage and the burden on families, the American Heart Association has recommended hypothermia for neuroprotection in post cardiac arrest care. 

However, current clinical hyperthermia cools the whole body instead of just the brain. Simple, effective and non-invasive methods to selectively cool the brain that can be readily used in and out of hospitals are not available.  

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The team has patented a simple and portable method where the brain is cooled by blowing cold air, generated using a vortex tube and compressed air, into the nostrils. The chilled blood from the nasal cavity collects and cools the blood in the internal carotid artery on the way to the brain, and so lowering the brain’s temperature while keeping body temperature normal.

“The grant is allowing us to collect validative data on the protective effect of brain cooling in limiting brain injury from cardiac arrest,” explains Dr. Lee. “The device is very convenient to use. It is compact and can be set up right by the bedside of patients in intensive care units.” 

Dr. Lee sees the device as having the potential to be used widely to limit brain injury following stroke, head trauma and sepsis. 

“This kind of investment in hospital-based research allows us to identify important clinical problems and find ways to solve them, working closely with research patients along the way.”

Multi-centre diagnostic performance of dynamic CT perfusion for functional assessment of multi-vessel coronary artery disease with dense coronary calcification
Dr. Aaron So 

Coronary artery disease (CAD) occurs when plaque forms in one or more coronary arteries of the heart. It is one of the leading causes of mortality and morbidity in the world. 

Patients with CAD can go to a cardiac catheterization laboratory where the narrowed coronary artery can be reopened using a catheter-based technique. However, this approach is invasive for the patient and costly for the system. Studies have shown that for various reasons not all patients benefit from this treatment.  

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“We have developed a new CT imaging technique that will help select the most appropriate CAD patients to undergo cardiac catheterization and revascularization,” says Dr. So. “Blood flow information in both the coronary arteries and the heart muscle are obtained simultaneously and non-invasively.” 

With the funding, they are testing the technique at several hospitals and national cardiovascular centres in Canada, China, Germany and Japan. With larger clinical studies in the future, they could determine the optimal diagnostic strategy for patient triage and reduce unnecessary procedures.

“Health research has been and will continue to be very important, with the commitment of patients and clinicians playing a crucial role in the success of medical research and advancement,” says Dr. So. “It’s important for the Canadian government to continue to support research in academic hospitals.”

He adds that the success of the CIHR grant application shows that Canadian researchers can be leaders in health research that benefits people around the world.

Filling Knowledge Gaps for the Success of Ontario Renal Plan 3
Dr. Matthew Weir

The Ontario Renal Network (ORN) is the agency responsible for distribution of funding for kidney care in Ontario. They have released three policy statements outlining strategic objectives for kidney care, with the most recent being the recently released Ontario Renal Plan 3 (ORP3).

“Within the strategic objective, gaps in our understanding of kidney disease have been identified as barriers to successful implementation,” explains Dr. Weir. “We have proposed a suite of 32 related retrospective cohort analyses designed using integrated knowledge translation to address those gaps.”

The Priority funding will help get the first projects underway and build momentum. “The ORP3 had extensive consultation with patients, families and other stakeholders. By supporting its successful implementation, our findings will have a direct and immediate effect on patients in areas that are a priority to them.” 

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