Backgrounder on funded projects

[ Press Release 2010-22 ]

The Vaginal Microbiome Project Team

Women's health and healthy pregnancies are intimately linked to the balance of bacteria and viruses that live in a woman's body. The fine balance of microorganisms in a woman's reproductive system is vitally important to the maintenance of health and the prevention of disease. For example, a healthy balance of bacteria can protect against infections such as Herpes and HIV, whereas an unhealthy balance can increase risk of infection in the uterus and fallopian tubes, and may ultimately result in cancer. We know that if the balance of bacteria in the vagina is not ideal in pregnancy, there are serious health consequences – one of which is risk of preterm birth. Preterm birth is one of the most serious complications facing infants, occurring in 7-8% of births in Canada but causing over 70% of newborn deaths and 50% of newborn health problems. This has been one of the hardest health problems to tackle worldwide with rates of preterm births increasing despite improvements in overall pregnancy care for women and their newborns. New advances in genomic research make it possible to study the composition of microbial communities in a women's reproductive system. Our team of researchers, lead by Dr. Deborah Money at the Women's Health Research Institute, and the University of British Columbia, Dr. Janet Hill at the University of Saskatchewan, Dr. Sean Hemmingsen at the National Research Council Canada, Dr. Gregor Reid at the University of Western Ontario, and Dr. Alan Bocking at the University of Toronto with many other collaborators will be conducting pioneering research to define a healthy vagina. This will ultimately lead to the development of novel diagnostic tools and interventions that restore and retain health. Ultimately, our work will lead to significant breakthroughs in the care of women in Canada and around the world.

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Influences of Host Genome on the Human Gut Microbiome: Studies in a Healthy Cohort Carrying Crohn's Disease Risk Alleles

Understanding the physiological and genetic bases of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a condition that causes inflammation and ulcers in the intestine and colon. IBD affects over 200,000 Canadians, often in childhood and adolescence. The cause of IBD is unknown, but current thinking suggests that it is due to a genetically determined, abnormal immune response to environmental challenges such as bacteria in the gut.

Dr. Ken Croitoru and his team are conducting a prospective study of healthy people genetically at risk of developing Crohn's disease, which is a type of IBD. The study, funded by the Crohn's and Colitis Foundation of Canada (CCFC) and termed "The GEM Project," is designed to help researchers identify a change in the gut bacteria or a change in the immune response in people who develop IBD, before they develop the disease. This may be the only way to identify the triggers that cause the disease and will help lead to new strategies for improved diagnoses and treatments.

Since Dr. Croitoru and his team believe that the composition of bacteria in the gut is influenced by genes known to confer risk of IBD, this newly funded Canadian Institutes of Health Research (CIHR) study will build on the CCFC GEM project by allowing the team to study the entire group of healthy individuals, many of whom carry changes in genes related to the development of Crohn's disease.

By assessing these individuals, Dr. Croitoru and his team can then study how specific genes influence the makeup of the entire population of gut bacteria (or 'Microbiota') in healthy people. The team can then sequence very large areas of the bacterial DNA. This approach will help identify and isolate specific organisms altered by the patients' genetic makeup, both in healthy people and in those with IBD.

Dr. Croitoru is a Clinician-Scientist at Mount Sinai Hospital, and a Professor of Medicine at the University of Toronto, Division of Gastroenterology.

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Modeling and mapping microbial diversity and function with marker genes, genomes and metagenomes

The human microbiome project aims to (1) characterize the diversity of types of bacteria in and on our bodies and (2) assess their various roles in health and disease, so that we might (3) learn better how to encourage the good bugs and discourage the bad. Achieving these interrelated goals requires better methods for identifying microbial types and predicting their activities. These must be based on sounder knowledge of underlying ecological and genetic mechanisms and processes. In the theoretical component of our project we will, through modelling and mapping of the ever vaster genomic and metagenomic databases, advance knowledge of mechanisms and processes. In the practical component, we will develop software for characterizing the diversity and predicting the impact of the many microbial communities we humans harbor. We believe this software will be of wide and immediate use to all microbiome scientists.
 
 

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Assessing the breadth and depth of cystic fibrosis-associated polymicrobial respiratory tract infections

Cystic Fibrosis (CF) is the most common fatal genetic disease among individuals of European descent, with mortality due to respiratory problems associated with repeated episodes of bacterial infection of the airways. The Canadian Institutes of Health Research Emerging Team Grant will allow us to use state-of-the-art genomic technologies to characterize the composition and dynamics of the microbial communities (bacterial, fungal, and viral) found in the CF lung during the progression of the disease and the initiation of antibiotic treatment. We will also assess the fine-level population dynamics of two key bacterial and one fungal species commonly associated with clinical exacerbations, study the diversity of metabolic profiles and antibiotic resistance found within these communities, and finally, the examine ethical issues related to the collection of patient data and samples for basic and clinical research. Our long-term goal is to establish guidelines to assist clinicians in the design and selection of therapies tailored for individual patients based on their clinical status and the specific nature of the infectious community.

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Impact of the Microbiota on Immune Development and Disease

There is increasing evidence that intestinal microbiota impact on immune development and disease. Allergic asthma is an ever-increasing problem in developed countries and affects up to 20% of all Canadians. Although there are many theories about the potential cause of asthma, the actual causes remain undefined. Recent evidence suggests that shifts in resident microbiota (normal flora) may play a significant role in atopic diseases such as asthma he so-called "hygiene hypothesis"). However, the role of the astrointestinal microbiota in asthma has not been explored experimentally, and no attempt has been made to identify microbial populations affecting asthma. We propose to assemble a strong interdisciplinary team to explore the contribution of the microbiota to immune development and the atopic disease asthma in both murine and human hosts. We will employ a well-characterized murine model of asthma to determine how the microbiota affects this disease by varying the microbiota using different antibiotics. The murine immune responses will be monitored following these microbiota shifts. Moreover, as part of the CHILD longitudinal cohort study, immune analysis will be performed on samples taken from children from birth until 1 year of age. In correlation with these studies, the composition of the intestinal microbiota will be characterized, and correlated with atopic diseases, as well results from the murine studies. Applied ethical questions associated with these results will also be studied. Collectively, these approaches will provide key information about the role of the intestinal microbiota in immune development and atopic diseases such as asthma. It will also bring together investigators with very different skills all working on a common problem. Ultimately this information could be used to develop new ways of treating asthma.

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Synergy in Microbiota Research

Our SyMBIOTA research team will study the impact of antibiotic use in newborn infants on the composition of intestinal microbiota at age 3 months and one year. Changes in infant microbiota will be evaluated for their effect on the development of allergy and asthma in children. This will be a study of 2,500 infants enrolled in the CIHR and AllerGen NCE-funded Canadian Healthy Infant Longitudinal Development (CHILD) study. Study objectives will be achieved through linkage of detailed data on antibiotic use in infants from provincial prescription database records with clinical data and bacterial profiles of their fecal samples. The composition of the infant's microbiota will be determined using DNA sequencing techniques. We have assembled an expert team of researchers across 5 Canadian universities, ranging from microbiologists, epidemiologists to immunologists. The proposed database linkage methods are novel and are being tested at the Winnipeg site of CHILD. They will also be used to train the next generation of researchers.

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Respiratory tract microbiome dynamics and the interplay of commensal bacteria with resident pathogens

The bacteria of the airways can be described as the good, the bad and the ugly. Most are good, protecting us from infections. However, there are pathogens present usually kept in check by other members of the community.

Dormant pathogens can also be provoked into behaving badly by seemingly good bacteria. Michael Surette is leading a team from McMaster University to define who's who in this complex community in order to understand how bacteria interact with each other and our immune system. In collaboration with Dr. Dawn Bowdish, an assistant professor of pathology and molecular medicine, and Dr. Jennie Johnstone, an assistant professor of medicine, (and Professors Tony Schryvers and Jim Kellner from the University of Calgary). Surette is working to shed light on how this bacterial community in the very young and in the elderly makes them more susceptible to respiratory infections.