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Widespread pesticide-use and diminished floral diversity in the environment have contributed to the worsening susceptibility of honeybees to infectious disease, threatening their support of adequate pollination of food crops. With the aim of tackling honeybee decline, a collaborative team including researchers at Lawson Health Research Institute and Western University have shown certain probiotic bacteria can be used to help ward off disease and promote overall hive health.

A new study published today in the journal ISME used two methods to deliver probiotics to hives within large commercial apiaries in California – a probiotic pollen patty and a spray-based delivery system – demonstrating a range of health benefits associated with the supplementation.

“We tend to think of bees just as organisms in themselves. But actually, bees have co-evolved with a lot of other organisms, the plants they feed on, and the bacteria that live inside their guts,” said Graham Thompson, biology professor at Western who has been studying honeybees for over two decades. “Those bacteria are functionally very important to the bees, for digestion and acquiring nutrients. It’s a symbiotic arrangement.”

Testing in a real-world setting

The teams have led research on three probiotic strains and shown they benefit honeybees, this latest research is the largest field study of its kind to date.

“Seeing an effect in the lab is one thing but seeing it in the real world is quite another,” said Thompson. “After treating the hives with probiotics using a BioPatty and a novel topical spray, we monitored them for all kinds of downstream effects and found lasting effects in their ability to withstand a variety of very common diseases.”

The probiotics developed by the researchers at Lawson and Western are specifically designed to enhance the honeybee’s core gut microbiota to boost their immunity and provide a viable alternative to antibiotics.

“Right now, most beekeepers treat their hives with antibiotics to prevent infectious disease,” said Brendan Daisley, a former PhD student at Western and now a postdoctoral researcher at the University of Guelph. “Unfortunately, there are a lot of negative side effects associated with treating hives with antibiotics, including development of resistance, and off-target health effects due to the drugs harming beneficial microbes, in addition to the pathogens of interest. We need different solutions to improve honeybee health, especially in a sustainable way, and we believe probiotics could be a feasible option.”

The researchers say part of the goal of testing the delivery methods of the probiotics is ensuring the research can be easily translated to the real world.

“A beekeeper has to go to the hive and be able to apply the probiotics, so we’re trying to make it easier for them to do that,” said Gregor Reid, professor emeritus at the Schulich School of Medicine & Dentistry, retired Lawson scientist and an international expert on probiotics. “We aim to make the solution practical, easy to use and proven to work, which is the essence of translational science. Not every bacterial strain works and even some commercial products have not been proven to be effective, so we can’t generalize. The key is selecting the right strains and proving they are effective in the real world.”

The team is working closely with SeedLabs to promote their research with major players in the beekeeping world.

Bee research on campus

The next phase of this research is continuing this summer on Western’s campus in the university’s experimental apiaries. Students Anna Chernyshova and Sophie Killam will be looking at how the probiotics influence the bees’ social behaviour, to understand what is referenced as the ‘gut-brain-axis’. In other words, how probiotic bacteria influence the brain.

“The idea is fascinating because it shows that the gut and the brain are actually communicating with each other through millions of bacteria releasing or inducing specific chemicals and neuro-compounds that influence the activity of the brain, including behaviour such as grooming or cleaning,” said Chernyshova, a PhD student in Biology. “Previously, this has only been studied at the individual level. And as we know, honeybees are social. So, we are looking to see if and how probiotic organisms can improve foraging and hygienic behaviour.”

The researchers are also comparing the hives treated with probiotics to those that have been treated with antibiotics to see which performs better. Using pollen traps, they can assess overall pollen production and determine which hives have bees that go to more diverse flowers. 

Killam, a master’s student in Thompson’s lab, is looking specifically at how these manipulations of the bees’ gut microbiomes influence where worker bees detect and remove diseased brood from the hive. She’ll spend the summer alongside the bees using video, radio tags and other observations to monitor the insects’ behaviour.

“I’ve really enjoyed taking care of the colonies here and am excited to do the field work this summer,” said Killam. “Bees are both an economically and ecologically important insect, for plants, animals and humans. And because they live in these large and close-knit colonies close to humans and industry, they are susceptible to disease. Looking at how we can support their health and wellbeing through natural mechanisms is really important.”

Researchers at Lawson Health Research Institute (Lawson) are developing a hand-held photoacoustic imaging probe to be used during breast conserving surgery to quickly and accurately verify if all cancerous tissue has been removed.

Surgeons currently do not have real-time technology to guide tumour removal during surgery.

Using current tools, there is a 20 per cent chance that cancerous cells will be left behind, risking recurrence and repeat surgery.

Breast cancer represents 25 per cent of all new cancer diagnoses in women and 13 per cent of all cancer related deaths in women. Treatment for breast cancer often requires either complete breast removal in severe cases, or surgical removal of the cancerous tumour in combination with other therapies. Removing only the tumour is called breast conserving surgery.

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Photoacoustic Screening

The new device is an extension of the photoacoustic screening (iPAS) technology developed in the laboratory of Dr. Jeffrey Carson, Principal Investigator and Lawson Scientist. The technique uses light and sound to capture 3D images of surgically removed breast tissue. Their studies show that iPAS can catch up to 75 per cent of missed tumour cells, decreasing the odds of failed surgery to five per cent.

Dr. Muriel Brackstone, Associate Scientist at Lawson, Head of the Breast Care Clinic at St. Joseph’s Hospital London, and Surgical Oncologist at London Health Sciences Centre, brings her clinical expertise to the project.

“With the first generation iPAS technology, we would remove the tumour, take it to the lab for imaging and wait to see if there was a rim of normal tissue around the removed tumour so we knew it was removed completely. The wait was anywhere from 20 minutes to an hour. During that time, the patient is under anesthesia, the surgical team is idle and precious OR time is being used,” explains Dr. Brackstone.

A hand-held tool that surgeons can use

Creation of a hand-held probe to be used in the operating room is the next step in the advancement of this new technology. Elina Rascevska, biomedical engineering student at Western University, recently joined the Lawson team to convert lab-based iPAS technology into a hand-held device.

“We have developed a prototype of the iPAS probe, and once we can verify the quality of the images it produces, we will give it to Dr. Brackstone to test in the OR,” says Rascevska.

The iPAS probe does not need a trained operator and would be used by the surgical team. Instead of imaging the removed tissue, it scans the surgical cavity in real time to give the team a faster and more accurate indication as to whether the cancerous tissue has been removed.

“If we can progress this technology to a point where physicians can use it as part of standard protocols, we will have reduced the amount of time each patient needs to spend in the OR, the amount of call-backs and repeat surgeries, and ultimately improve quality of life for patients with breast cancer,” adds Dr. Carson.

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Researchers at Lawson Health Research Institute are the first in the world conducting a clinical trial to test a triple intervention aimed at treating Mild Cognitive Impairment (MCI) and delaying the onset of dementia. The Mobility, Exercise and Cognition (MEC) team will be incorporating physical exercises, cognitive training and vitamin D supplementation to determine the best treatment for improving mobility and cognition.

“We have learned the brain processes involved in motor-control - for example how a person walks - and cognition - for example how that person solves a problem - share similar locations and networks in the brain,” explains Dr. Manuel Montero Odasso, Lawson Scientist and Geriatrician at St. Joseph’s Health Care London. “Problems with mobility are connected to lowering function in the mind, and so can be a good indicator of future progression into dementia.”

Dr. Montero Odasso is also an Associate Professor in the departments of Medicine and Epidemiology and Biostatistics at the Schulich School of Medicine & Dentistry, Western University. 

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MCI is an intermediate stage between the expected cognitive decline of normal aging and the more serious decline of dementia. It can involve problems with memory, language, thinking and judgment. While many older individuals experience decline in both mobility and cognition, each are assessed and treated separately with no specific recommendations available for physicians.

The SYNERGIC Trial will combine physical exercises, cognitive training and vitamin D to test how these interventions work together to improve cognition in older adults at risk for dementia. The trial is targeting cognitive decline at the earliest stage, individuals with MCI, where interventions are more likely to have an effect and can be monitored.

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Dr. Montero Odasso explains that both physical and cognitive exercises have shown promising effects for maintaining cognition, while vitamin D deficiency is associated with cognitive decline. A key feature of this trial is that participants will receive individualized and progressive training.

“By delaying declines in cognition, we can improve a person’s quality of life. This research will help to support a more comprehensive preventative treatment with clinical guidelines for physicians whose patients are at risk of developing dementia,” states Dr. Montero Odasso. “Even more, each one year delay of progression to dementia in older individuals at risk has the opportunity to save billions of dollars for the Canadian health care system.”

Individuals over 60 years old with mild cognitive impairment without dementia are eligible for this clinical trial. Those interested in participating are encouraged to contact Research Coordinator Alanna Black at 519.685.4292 ext. 42179.

Participants will be asked to complete a routine of exercises and cognitive training three times a week for six months, with one final assessment at 12 months. The main site for the study is Parkwood Institute with physical exercises taking place at the Labatt Health Sciences Building at Western University, in Dr. Kevin Shoemaker’s Laboratory for Brain and Heart Health.

This study has been funded by the Canadian Consortium on Neurodegenerative in Aging (CCNA) which represents Canada-wide research aimed at enhancing the quality of life and services for individuals diagnosed with a neurodegenerative disease. The MEC team in London, led by Dr. Montero Odasso, includes expert researchers in the field of mobility who aim to develop common assessments for the interaction of cognition and mobility for older people to aid as a diagnostic tool for detecting dementia. 

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As we continue to live with a COVID-19 pandemic, patients will need good treatment options.

Hospital researchers in London, Ontario, through Lawson Health Research Institute, are testing treatment options for patients who have been hospitalized from a COVID-19 infection, often for severe symptoms.

During the peaks of the COVID-19 pandemic, there were concerns of a global drug shortage when it came to IV sedatives for patients needing ventilation. Through funding from the Government of Ontario’s COVID-19 Rapid Research Fund, a team of Ontario researchers studied whether inhaled sedatives could replace those that are delivered through IV.

“In addition to easing the burden on IV stocks, the inhaled sedatives have additional benefits,” says Dr. Marat Slessarev, a Critical Care Physician at LHSC. “They may reduce inflammation in the lungs and shorten the duration of sedation because they are eliminated from the body faster than IV sedatives.”

Dr. Slessarev, also a Scientist at Lawson, adds that using inhaled sedatives could also be safer for severe COVID-19 patients, who in many cases are on a ventilator for a long time. “When using IV sedatives, they can accumulate and metabolize with accumulation. This can leave the patient with the potential of developing kidney issues because it is hard to dispel them quickly.” 

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Dr. Marat Slessarev, Critical Care Physican at LHSC and Lawson Scientist

To date, around 800 patients across ten hospital sites have been enrolled in this trial, with the hopes of getting more hospital sites on board as the clinical trials continue.

• Read more about this multi-centre clinical trial.

A majority of people with severe COVID-19 infections in critical care end up developing sepsis, which is a potentially life-threatening condition that occurs when the body's response to an infection damages its own tissues. 

“An inflammatory response is what the body uses to fight an infection, but sometimes it is more than necessary and it causes damage to the organs and the body,” explains Dr. Claudio Martin, a Physician in the Intensive Care Unit (ICU) at London Health Sciences Centre (LHSC). “This is why a patient with a severe COVID-19 infection caused by a virus can get sepsis.”

Dr. Martin, who is also an Associate Scientist at Lawson, began studying the use of a human protein called Annexin A5 as a potential treatment for COVID-19 patients with sepsis. “It can work in two ways. The annexin may coat injured cells and reduce the inflammatory response. Or, the injured cells and exposed proteins trigger the clotting mechanism in the body. Those with COVID-19 could get blood clots in the brain and the lungs, and using annexin may improve their outcomes.”

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Dr. Claudio Martin, Critical Care Physician at LHSC and Lawson Scientist

Currently, a clinical trial using Annexin A5 on severe COVID-19 patients is underway at LHSC to look at the efficacy of using this human protein.

• Read more about this clinical trial.
   

The COVID-19 virus is also known to cause respiratory failure, prompting Dr. Jim Lewis, Respirologist at St. Joseph’s Health Care London and Scientist at Lawson, to investigate the use of pulmonary surfactant as a potential treatment for these patients.

Bovine Lipid Extract Surfactant Suspension (BLES) is a pulmonary surfactant manufactured in London, Ontario. It’s currently used worldwide to help improve lung function in premature babies. Now, it is being studied with COVID-19 patients experiencing respiratory failure.

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Dr. Jim Lewis, Repirologist at St. Joseph's Health Care London and Lawson Scientist 

“We know that patients who have injury to their lung and require ventilation have inflammation in the airways of their lungs. Surfactant is a homogeneous layer of lipids and proteins that line the lungs to allow us to breath with minimal effort,” explains Dr. Lewis. “If we gave these patients surfactant as soon as possible after they were put on a mechanical ventilator, it may have some benefit in improving their outcome and getting them off the ventilator sooner.”

Dr. Lewis and his team conducted a clinical trial using pulmonary surfactant with ten critically ill COVID-19 patients and initial results have shown patient safety and efficacy.

• Read more about the BLES study.
   

Another team of hospital researchers turned to using modified dialysis machines to offer treatment options to those with severe COVID-19 symptoms. Nephrologist at LHSC, Dr. Chris McIntyre, was the first in the world to modify a dialysis device to treat a patient with COVID-19.  The device gently removes a patient’s blood, modifies white blood cells, and returns them to fight hyperinflammation.

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Dr. Chris McIntyre, Nephrologist at LHSC and Lawson Scientist

“It was quick.  We went from the initial idea to the approvals, creating the device and appointing the first patient within 40 days,” says Dr. McIntyre who is also a Scientist at Lawson. “After the first 12 patients, we found that those treated with the device needed significantly less drugs to maintain their blood pressure. We were able to deliver the treatment for all the patients – none of the treatments failed and we had no safety issues.”

Dr. McIntyre is now looking into using this form of therapy for chronic dialysis patients to help modify organ injury.

• Read more about his COVID-19 research with modified dialysis machines.

Quickly after the COVID-19 pandemic began to grip the world, Lawson Health Research Institute responded with action. Lawson is the research arm of London Health Sciences Centre (LHSC) and St. Joseph’s Health Care London. With hospitals focused on providing excellent patient care in the face of an unknown virus, hospital researchers in London, Ontario began critical COVID-19 studies.

“A lot was unknown during the first wave of the pandemic. Any research that wasn’t essential was put on hold. At the same time, we had people with different expertise coming together with different perspectives to see how we could better understand the SARS-CoV-2 virus and the COVID-19 infection,” explains Dr. David Hill, Lawson Scientific Director and VP, Research at LHSC and. St. Joseph's. “Our hospital researchers formulated ideas and very quickly came up with research proposals. These were fast tracked through our processes and within two months we approved over 50 new studies surrounding COVID-19.”

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Dr. David Hill, Lawson Scientific Director and VP, Research at LHSC and. St. Joseph's

Some of these studies were clinical trials, which are research studies performed with people. Many patients from London hospitals get involved as patient participants and when COVID-19 hit, many agreed to be a part of this important research.

“We saw the pandemic happening across the world, and suddenly it was happening here in London. This has probably been the biggest challenge of my career,” says Carol Young-Ritchie, Executive Vice President at LHSC. “We had to look at many of our processes and how we were doing things, and adjust appropriately and nimbly.”

Young-Ritchie adds that as the hospital continued to admit a growing number of COVID-19 patients, a strong focus on research was needed. “It was absolutely critical and important for LHSC as a leader and academic centre to contribute to our collective knowledge. We needed to keep that research going and although it has been challenging, it has also taught us to be innovative.”

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Carol Young-Ritchie, Executive Vice President at LHSC

The same focus was happening at St. Joseph’s Health Care London, with health care providers and researchers finding ways to improve care and outcomes for patients who had contracted the virus. “COVID-19 research through the hospital has been incredibly important,” says Karen Perkin, Vice President of Patient Care at St. Joseph’s. “We had researchers busy looking at the impacts of COVID-19. We had patients on ventilators and we were trying to understand that more. We also had research looking at the impacts for staff members looking after patients. All important, helpful knowledge as we move forward.”

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Karen Perkin, Vice President of Patient Care at St. Joseph’s

Hospital research in London through Lawson is proudly affiliated with Western University. At Western’s Schulich School of Medicine & Dentistry, the new state-of-the-art Imaging Pathogens for Knowledge Translation (ImPaKT) Facility was the perfect environment to conduct COVID-19 research.

“ImPaKT is a special containment facility where research on viruses like SARS-CoV-2 can be done safely,” says Dr. David Litchfield, Vice Dean of Research and Innovation at Schulich Medicine & Dentistry. “It has become a focal point for dozens of studies involving research through Schulich Medicine & Dentistry, as well as partners from the hospitals and other academic institutions and industries.”  

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Dr. Litchfield adds that collaboration between hospital partners and scientists has been the key to successful COVID-19 research. “This collaboration has enabled advances leading to new diagnostic testing for COVID-19, as well as studies using MRI or related imaging tools to investigate long-term impacts of the infection on individuals.”

The rapid research response to COVID-19 couldn’t have happened without community and foundation financial support. “Funding support from our hospital Foundation is something we are so grateful for,” says Perkin, referring to St. Joseph’s Health Care Foundation. “They came right out at the beginning and asked how they could help, as did our donors.”

LHSC’s London Health Sciences Foundation and Children’s Health Foundation were also pivotal in research funding during the pandemic. “Funding is a crucial part to how we do hospital research and the Foundations have been important partners in making sure our research continued,” says Young-Ritchie.

As the pandemic continues, so does the research within our community. Hospital research has already improved diagnostics, treatments and patient outcomes related to COVID-19 and helped people all around the world.

“If you look at some of the achievements that have occurred in just a little more than a year, we have had a number of landmark publications on ways to diagnose COVID-19 compared to other respiratory disorders,” notes Dr. Hill. “We have had many rapid advances and it can take a crisis to bring out the best in people. Then things come together quickly, such as expertise, talent and money – and the job gets done.”

• Lawson COVID-19 Updates