Researchers at McMaster University’s Farncombe Family Digestive Health Research Institute are investigating how changes in the gut resident bacteria can lead to disease and developing strategies for diagnosis, treatment, and prevention.
Researchers are increasingly discovering the importance of our gut microbiome to our physical and mental health. Scientists and clinicians at McMaster University’s Farncombe Family Digestive Health Research Institute are making great strides in understanding how changes in the gut microbiome can lead to disease and are developing new strategies for the diagnosis, treatment, and prevention of digestive diseases.
Following the discovery that a single resident bacterium, Helicobacter pylori, could cause peptic ulcers and gastric cancer, McMaster University’s Intestinal Disease Research Program turned its attention toward the microbiome. In 2003, it opened Canada’s first germ-free facility, which enables researchers to study mice that either have no microbes or have a prescribed microbial community, thus allowing the study of how resident bacteria interact with the host (in photo below). In 2008, the program became the Farncombe Family Digestive Health Research Institute, focusing on the role of the microbiome in health and disease.
Our small and large intestines house trillions of bacteria, fungi, and viruses, which together are referred to as the microbiome. The microbiome is an integral part of us and helps maintain health. It’s influenced by genetics, stress, diet, and antibiotic exposure, and under certain circumstances can predispose us to disease.
A major strength of the Farncombe Family Digestive Health Research Institute is its multidisciplinary approach, which involves collaboration between clinicians, clinician-scientists, and basic scientists. “This is important because we can conduct pre-clinical studies in the laboratory, take the findings, and test them in our patients. We can also take observations from our patients and investigate these problems in the lab. This, bidirectional translational research capability is of great benefit in understanding disease,” says Dr. Stephen Collins, Director of the Farncombe Family Digestive Health Research Institute and Professor of Medicine at McMaster University.
Fecal transplantation to treat ulcerative colitis
Professor of Medicine, McMaster University
Director of Clinical Research, Farncombe Family Digestive Health
Research Institute & Professor of
Medicine, McMaster University
One important study at the institute is led by Dr. Paul Moayyedi, Director of Clinical Research at the institute and Professor of Medicine at McMaster University. “It was believed that ulcerative colitis and Crohn’s disease were autoimmune diseases, caused by your own immune system attacking the gut. All therapies, like steroids and biologics, were aimed at suppressing the immune system,” he says.
But Dr. Moayyedi wanted to study what was causing this immune reaction, investigating how microbes might be driving it. He looked to fecal transplantation, which is the transfer of stool from a healthy donor into the gastrointestinal tract, usually to treat C. difficile.
Dr. Moayyedi’s lab, in collaboration with microbiologist Dr. Michael Surette, ran a randomized trial replacing the bacteria in the colon of patients with ulcerative colitis with healthy bacteria. The study found that with a weekly transplant for eight weeks, about 25 percent of people will go into remission. These results are comparable to the effects of biologic therapy.
“This proves that if you alter gut bacteria, in some people, this can alter the disease. This is very strong evidence that ulcerative colitis is driven by an infectious agent in your colon,” says Dr. Moayyedi. “We’re not perfect yet, but if we understand better what we’re trying to modulate, we can effect a cure for this disease. That will take time, but we already have a therapy that could be an alternative for some people.”
Connection between gut microbiome and mental health
Professor of Medicine, McMaster University
Dr. Premysl Bercik, a researcher at the institute and Professor of Medicine at McMaster University, is studying gut bacteria’s impact on mood and mental health.
“Animal data demonstrates that the behaviour of germ-free mice differs from conventionally-raised mice, who are born and raised with bacteria, along with differences in brain chemistry and structure,” he says, adding that there’s increasing evidence that microbial profiles differ between patients with anxiety and depression compared to people with no mood disorder. Fecal transplantation from patients into germ-free mice has also been found to induce anxiety and depressive-like behaviour.
In Dr. Bercik’s pilot clinical study, patients with irritable bowel syndrome (IBS) who also had depression and/or anxiety were treated with probiotic bacterium B. longum NCC3001. This treatment improved IBS symptoms and also improved depression scores after six weeks, which was accompanied by changes in activity of several brain regions that control mood and anxiety.
Gut microbes’ interactions with the food we eat could determine disease
Dr. Elena Verdu
Associate Director, Farncombe Family Digestive Health Research Institute & Professor of Medicine, McMaster University
Dr. Elena Verdu, Associate Director of the institute and Professor of Medicine at McMaster University, studies gut inflammation in inflammatory bowel disease (IBD) and celiac disease. She explains that in celiac disease, gluten damages the lining of the gut in people with certain genes. But these are common genes, so Dr. Verdu studied why celiac disease occurs in some people and not in others. Her lab looked at how gut microbes could determine whether or not you’ll get the disease.
“We found that people with celiac disease have certain microbes that feed on the gluten they eat, breaking down the gluten proteins into smaller pieces called peptides and those peptides, are better absorbed through the gut lining and can activate immune cells in celiacs,” she says. “While in most people, without the genes, this doesn’t cause any problems, in a person with the risk genes it can lead to a higher susceptibility to develop the disease.”
Dr. Verdu says that there’s a crosstalk between our gut microbes, the foods we eat, and the cells in our body. “When those interactions are equilibrated, they contribute to a healthy state,” she says. “But when there’s an imbalance in this interaction, then gut microbes and their metabolites can cause inflammation and contribute to IBD and celiac disease.”
Integrating scientific fields to increase understanding
Director, Farncombe Family Digestive Health Research Institute & Professor of Medicine, McMaster University
“We share our diet with our microbial partners,” says Dr. Stephen Collins, Director of the institute and Professor of Medicine at McMaster University. “That means microbes can alter what we eat, for better or worse. We also recognize that diet is the most important factor that shapes our gut microbial community. We believe we can modify this community to promote health or treat disease by changing certain components of our diet. The way forward is to adopt an approach that integrates nutritional science with microbial and intestinal research to optimize health and manage chronic conditions within and beyond the gut.”