Dr. Stephen M. Collins was educated at The London Oratory School and obtained his medical training at University College, London and at The Westminster Hospital Medical School, London UK. He later specialized in internal medicine at the University of Leicester,UK. He trained in gastroenterology at McMaster University in Canada before completing 3 years of research training in cell biology at the Digestive Diseases Branch of the National Institutes of Health (NIH) in Bethesda, Maryland USA. He has been a staff gastroenterologist at McMaster University since 1981 and became the Director of the Intestinal Diseases Research Unit from 1983-1993, and Head of the Division of Gastroenterology from 1993-2006.
His basic and clinical research has addressed the pathophysiology of functional intestinal disorders and inflammatory bowel diseases. Initially his work focused on brain-gut interactions in the context of these diseases, examining mechanisms underlying the influence of stress and behavior on gut function and intestinal inflammatory processes. He next focused on acute enteric infection as a trigger for functional intestinal disorders and became interested in the role of the intestinal microbiota in these disorders. Currently, his work examines the bidirectional interactions between the intestinal microbiota and the gut-brain axis in health and disease. Ongoing work addresses mechanisms underlying the ability of the intestinal microbiota to alter brain function and behavior. His work has generated over 250 peer-reviewed publications including papers in Nature Medicine, Nature Communications, Nature Reviews Microbiology, Lancet, JCI, Gastroenterology and Gut, generating over 18,000 citations and an h index of 73 (Google Scholar). He has received continuous funding from The Canadian Institutes of Health Research for over 25 years.
He is past president of the Canadian Association of Gastroenterology and has served on advisory committees for Crohn’s and Colitis Foundation of America and the Crohn’s and Colitis Foundation of Canada. He has served on review panels for the Canada Gairdner Award for Biomedical Research and the Canada Wightman Award. He established and directs the Farncombe Family Digestive Health Research Institute at McMaster University where he is also the Associate Dean for Research in the Faculty of Health Sciences. He is a Fellow of the Royal Society of Canada and holds the title of Distinguished University Professor at McMaster University.
Overview of Research Program
Dr. Collins’ research is in collaboration with his colleague, another clinician-scientist, Dr. Premsyl Bercik and focuses primarily on the pathogenesis and pathophysiology of Functional Gastrointestinal Disorders (FGD), with a focus on microbes and the Irritable Bowel Syndrome (IBS). IBS is a clinical descriptor that encompasses several chronic abdominal symptom-complexes that occur in the absence of any discernible structural abnormality; they are disorders of GI function that includes motor, sensory and barrier functions. They are accompanied by psychiatric co-morbidity in up 60% of patients, prompting the suspicion that they are “psychosomatic disorders”. They have challenged this perception by investigating peripheral (extra-CNS) mechanisms that can trigger and or maintain the dysfunction that characterizes IBS. They focus on the role of pathogenic microbes as triggers and commensal microbes as putative agents that maintain chronicity of these conditions, and on and immune activation/low grade “inflammation” as the transduction mechanism underlying gut dysfunction.
Their research has provided proof of concept that the mucosal immune system modulates function in the intestinal sensory-motor apparatus and promoted the hypothesis that activation of the mucosal immune system, resulting in non-destructive low grade “inflammation” plays a pathophysiological role in at least a subset of patients with FGD. They’ve developed a murine model of long-term gut dysfunction following transient enteric infection and showed that this was maintained by low-grade inflammation. Translating this, they followed patients in UK and in Walkerton, Ont., with acute gastroenteritis and established that up to 30% develop FGD. Their genotyping study showed that polymorphisms in genes encoding bacterial recognition, barrier function and cytokine secretion were associated with the development of post-infectious IBS. Their epidemiological studies in Walkerton revealed that some patients remained symptomatic for as long as 8 years post infection, raising questions regarding mechanisms that sustain chronic gut dysfunction.
Their interest then turned to the intestinal microbiota and they showed that disruption of the microbial composition of the gut (“dysbiosis”) could alter visceral pain responses and induce low-grade intestinal inflammation in a pre-clinical model. They also found that experimental dysbiosis could alter brain chemistry and behavior in their pre-clinical model. Moreover, they were able to transfer components of behavioral phenotype between different mouse strains using fecal microbiota transplantation. Together these findings prompted consideration of a microbiota-got-brain axis. This axis may be relevant to the high prevalence of psychiatric co-morbidity in IBS patients.
Recent work in preclinical models has shown that early life stress can induce changes in the microbial composition of the gut, and that the intestinal microbiota acting with host factors, is critical for the expression of depression in a preclinical model. Together these findings indicate that the proposed microbiota-gut-brain axis is bidirectional.
Currently the research of Dr. Collins and Bercik is directed at addressing the mechanisms by which the intestinal microbiota influence gut and brain function, and how selected probiotic bacteria might ameliorate intestinal and brain function in pre-clinical and clinical models.
CIHR Foundation Grant “Microbiome and the gut-brain axis: A translational approach for intestinal and neuropsychiatric disease” 2015-22. Bercik P & Collins SM Co-PI’s.