2018 Proof-of-Principle – Results

The W. Garfield Weston Foundation Awards $3.75 M to Support Canadian Microbiome Research.

February 1st, 2019

The microbiome has become an area of intense interest in health research. In the span of a decade it has come to be suspected of influencing diverse aspects of human health and disease, including gastrointestinal maladies, neurological conditions, immune function, obesity, aging, amongst many others. And while much is still unknown, it is becoming increasingly clear that our communities of microbial passengers play a crucial role in bodily function and health.

In an effort to bring this important area of science closer to application, The W. Garfield Weston Foundation is pleased to announce the awarding of $3,750,000 to Canadian scientists undertaking innovative research on the microbiome. The funds are supporting twenty-five research teams at Universities across Canada in their efforts to develop new approaches that leverage our microbes to deliver health benefits, and prevent or treat disease.

“The microbiome is one of the most exciting areas of health research” said Mark Mitchell, Chair of the Weston Family Microbiome Initiative. Virtually every day brings new studies further emphasizing its importance in health and disease. What’s more, the field is challenging us to think increasingly holistically about health, nutrition, disease and lifestyle. Canada is fortunate to have a wealth of talented scientists working in this space and is well-positioned to play an integral role in furthering our understanding of this important aspect of biology towards improving health.”

 

Project Descriptions


 

Control of fungal expansion during early-life antibiotic treatment to prevent asthma development.
Dr. Marie-Clair Arrieta, University of Calgary
When patients are treated with antibiotics it can lead to an overgrowth in fungus in the gut. The increase in fungus has been found to be correlated with increased asthma risk and other early-life immune responses. The project will test the probiotic potential of the yeast, Saccharomyces boulardii, to prevent the overgrowth of fungus. This yeast has been shown to limit the growth of a number of problematic fungi.

 

Neuroactive and immunomodulatory molecules of bacterial origin involved in gut-brain axis communication.
Dr. Premysl Bercik, McMaster University
The project will develop a new tool that simulates the intestine and enables rapid testing of the influence of probiotics on the intestinal environment. The authors expect to uncover useful molecules and postbiotics that mediate the beneficial effects of probiotics on the host. This will not only provide insight into the mechanism of probiotics but also provide new directions for developing other useful microbiome-based therapies.

 

Enhancing the effectiveness of probiotic treatment in allergy.
Dr. John Bienenstock, St. Joseph’s Healthcare Hamilton
The research team has shown that specific microbes can reduce symptoms of allergy. This effect is thought to be mediated by the production of microvesicles (MVs), a biological tool that bacteria use to communicate with other cells. The team will test this theory by examining the effect of probiotics supplemented with MVs on allergy symptoms in the intestine and respiratory tract.

 

Use of novel human milk prebiotics to improve the quality of life for neurogenic bladder patients.
Dr. Jeremy Burton, University of Western Ontario
Spinal cord injury (SCI) is a life-changing neurologic diagnosis that is known to affect multiple body systems, including bowel and bladder function. Urinary Tract Infections (UTIs) and impaired bowel function are a common complication of SCI. Researchers will look to use two prebiotic sugars derived from human milk to modulate intestinal bacteria in order to repair bowel movement and reduce the frequency of UTIs.

 

Restoring lost anaerobes in ICU-acquired dysbiosis.
Dr. Bryan Coburn, University Health Network
Critical illness leads to a significant disruption of the intestinal microbiome – the organisms that normally live in our intestinal tract. This disruption has been linked to negative health outcomes in critical illness and other diseases.  The researchers are testing different types of probiotic bacteria to see if they are able to protect against common systemic infections in patients in intensive care units.

 

A yeast synthetic biotic platform for microbiome remediation.
Dr. Brian Coombes, McMaster University
In a new collaborative project between McMaster University and the University of Montreal, researchers are engineering probiotic yeast that produce antibodies to target specific bacteria in the microbiome. This approach can allow precision editing of the microbiome to eliminate disease-causing pathogens without damaging the healthy microbiome. Initial studies using this system will target the microbes and inflammatory responses associated with Crohn’s disease.

 

Probiotics as a strategy to treat fungal infections.
Dr. Leah Cowen, University of Toronto
The project will identify specific chemicals produced by probiotic bacteria (Lactobacilli) which are able to impair the ability of the microbe Candida albicans to cause vaginal yeast infections. If successful, the authors will have identified a promising avenue for developing a new therapy that improves women’s health and is superior to existing probiotic treatments for yeast infections.

 

Influence of prebiotics on intestinal permeability.
Dr. Levinus Dieleman, University of Alberta
Intestinal permeability, or so-called ‘leaky gut,’ has been associated with Crohn’s disease. The researchers have found that first-degree relatives (FDR) of Crohn’s patients also suffer from leaky gut. The research team will examine the ability of the prebiotics inulin and oligofructose to improve leaky gut in FDR and identify the potential mechanism of action, which is suspected to relate to changes in the microbiome.

 

Treating anxiety in Parkinson’s Disease with a multi-strain probiotic – a randomized, controlled trial.
Dr. Brett Finlay, University of British Columbia
The project will conduct a clinical trial to determine the effect of a commercial probiotic, comprising multiple strains of beneficial bacteria, on anxiety in patients with Parkinson’s Disease (PD). The study draws on previous work that has demonstrated that patients with PD have altered gut microbiota and suffer from gastrointestinal dysfunction, and research that has demonstrated probiotics can have beneficial effects on mood disorders.

 

Prebiotics to enhance immunotherapy response in urological cancers.
Dr. Yves Fradet, Université Laval
Immunotherapy has become one of the most effective treatments for cancer. Unfortunately, it does not work for everyone. Recent breakthroughs have demonstrated that the composition of intestinal microbiota can have a decisive impact on the individual’s response to immunotherapy. Dr. Fradet and his colleagues will study the ability of some specific prebiotics to enhance the effectiveness of immunotherapies for treating bladder cancer through modulating the microbiome.

 

Profiling of the gut microbiome in children with Prader-Willi Syndrome: a fiber intervention to target hyperphagia.
Dr. Andrea Haqq, University of Alberta
Prader-Willi Syndrome (PWS) is the most common syndromic form of childhood obesity, accompanied by hyperphagia – an insatiable appetite. Previous studies indicate that the microbiome may play a role in the hyperphagia, obesity and metabolic abnormalities of PWS. The researchers will conduct a clinical trial to determine if a mixture of fibres (including acacia gum, resistant starches and whole foods) can reduce hyperphagia and improve metabolism in children with PWS through modulation of their microbiota.

 

A study comparing efficacy of lyophilized stool vs lyophilized fecal filtrate in the treatment of recurrent C. difficile.
Dr. Dina Kao, University of Alberta
Fecal Microbial Transplantation is highly effective in preventing Clostridium difficile recurrence. However, it is crude, archaic, and there are concerns about the long-term health effects of transferring live fecal bacteria between people. The project will determine if live bacteria are in fact required for the beneficial effect of FMT by conducting a clinical trial for treating C. difficile with a sterile FMT mixture from which all live bacteria have been removed.

 

FP2 – Feasible Prenatal Probiotics
Dr. Tobias Kollmann, University of British Columbia
Recent studies have shown that the administration of the probiotic Lactobacillus plantarum (Lp) to newborns in the first week of life dramatically reduces the risk of sepsis. This strategy, however, is ineffective for babies that are septic prior to birth or within the first week of life. The research team seeks to administer these probiotics to pregnant mothers in an effort to colonize fetuses prior to birth, thereby protecting them from the risk of sepsis.

 

Development of a new prebiotic from cranberry and camu-camu to alleviate obesity-linked diseases .
Dr. Andre Marette, Université Laval
The researchers are looking at the combined efficacy of two classes of polyphenols (proanthocyandidins and ellagitannins) from cranberries and camu-camu (a cherry-like Amazonian fruit) presenting prebiotic effects. These prebiotics are suspected of having benefits for controlling obesity and improving liver health. The researchers predict that there will be beneficial synergy when both prebiotic polyphenols are used in tandem, which will significantly improve diet-induced obesity.

 

Investigating the influence of intestinal microbes in promoting or preventing Autism Spectrum Disorder.
Dr. Kathy McCoy, University of Calgary
Mounting evidence suggests that the microbiome may play a role in Autism Spectrum Disorder (ASD). Utilizing bacteria isolated from children with ASD before and after treatment, this project seeks to identify specific bacterial species that promote or inhibit ASD using mouse models for the disease. In addition, it aims to identify the mechanisms by which these bacteria alter disease to determine if targeting these bacteria could be used to treat ASD.

 

Microbiome-based precision medicine in Inflammatory Bowel Disease.
Dr. Alain Stintzi, University of Ottawa
Studies have suggested that alteration of the microbiota contributes to Inflammatory Bowel Disease (IBD). The team will test Resistant Starches (RS) in treating IBD via their ability to restore a healthier microbiota and beneficial microbial functions. The influence of RS on microbes varies from individual-to-individual. The team will develop a personalized RS therapy by analyzing each patient’s microbiome prior to treatment with RS.

 

A clinical trial to evaluate the safety and efficacy of FMT in a population with Major Depressive Disorder.
Dr. Valerie Taylor, University of Calgary
There is a growing wealth of evidence suggesting that the microbes of the gut can have profound effect on the brain. The study will conduct a novel clinical trial to assess the effectiveness of  fecal microbiota transplantation (FMT), delivered via capsules, as a treatment for major depressive disorder in adults. This is based on a large body of animal work delineating the gut-brain connection and showing, among other things, that anxiety and depression can be induced in mice using microbes transferred from human patients suffering from these ailments.

 

Bacterial heat shock proteins as immune regulators in Crohn’s disease.
Dr. Johan Van Limbergen, Dalhousie University
The researchers have identified a bacterial protein that is linked to remission of Crohn’s disease and is suspected to be involved in the modulation of intestinal inflammation. The team will identify the bacterial species that produce this protein towards developing microbiome-focused therapies that can be used for the treatment of Crohn’s disease.

 

 

Disease prevention in specific-pathogen free relapsing-remitting experimental autoimmune encephalomyelitis (SPF RR-EAE) mice through gut microbiota modulation.
Dr. Jens Walter, University of Alberta
The project will test the therapeutic effect of bacterial species in preventing disease in a well-established mouse model for multiple sclerosis (MS), a suspected autoimmune disease. The study is innovative as the bacteria that will be studied were isolated from non-industrialized communities in Papua New Guinea that are known to have a low prevalence of MS. The strains included are known to modulate immune responses. Preliminary work in the mouse model for MS indicated that one of these bacteria protected mice from progression of the disease.

 

Improving commercial kefir through the use of traditional organism starter cultures.
Dr. Benjamin Willing, University of Alberta
Traditional kefir provides diverse health benefits, including reduced weight gain and improved cholesterol levels, which are attributed to the presence of bacteria and yeast that arise from the unique fermentation process. Commercially produced kefir, however, lacks many kefir-specific microbes and does not deliver the same health benefits. This project will utilize a commercially scalable method the research team has developed to produce kefir that contains the correct microbes and reproduces the benefits of traditionally-prepared kefir. They will also test the cholesterol lowering effect of their new kefir in a randomized control trial.