SCIENCE & RESEARCH

Gut feeling

About 18 years ago, Dr. Charles Bernstein returned to Winnipeg with some new ideas about how to help people who suffer from Crohn's disease and colitis. Today, he heads a program that has quietly become a world leader of research into inflammatory bowel disease.

Dr. Charles Bernstein
Dr. Charles Bernstein
Read more

What is inflammatory bowel disease?

IBD Basics

Bio: Dr. Charles Bernstein

About the IBD Clinical and Research Centre

BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, March / April 2011

It was the fall of 1988, and John Harvie was entering the prime of life.

The 28-year-old Winnipeg man was in excellent physical condition, married with a young family, and embarking on a promising career with the Canadian Forces as an airframe technician.

And then his dream life slowly started to slip away. First, he lost his appetite. Then he started to lose weight because he couldn't keep a meal down. As his health deteriorated, he started to experience excruciating stomach pain, diarrhea and incontinence. It was not a pretty sight, recalls Harvie. "I was literally projectile vomiting."

Eventually, Harvie was diagnosed with Crohn's disease, a form of inflammatory bowel disease (IBD). The condition causes the body's immune system to go into overdrive, attacking the otherwise healthy lining of the digestive tract. The disease left parts of his colon, small intestine and rectum inflamed and covered with ulcers.

Harvie would spend the next few years struggling against the condition, but for the most part his illness would have the upper hand. "I had really debilitating pain - ongoing, endless pain. I went from a healthy 180-pound man down to 119 pounds."

Physically unable to meet the demanding requirements of his job with the Armed Forces, Harvie was placed on long-term disability. Simply put, Crohn's was stealing the best years of his life.

By 1994, frustrated, tired and losing hope, Harvie landed in the care of Dr. Charles Bernstein. At the time, Bernstein was just settling in as the head of the newly created Inflammatory Bowel Disease Clinical and Research Centre in the Faculty of Medicine at the University of Manitoba's Bannatyne Campus. A year earlier, Bernstein, who had been a professor at UCLA in Los Angeles, had returned to Manitoba to head up development of the Faculty of Medicine's academic gastroenterology program.

Harvie could not have known it back then, but that first meeting with Bernstein would mark the beginning of a remarkable journey, one that would ultimately change his life for the better.

Although he was barely out of training, Bernstein had some new ideas about how to help people like Harvie. Under his leadership, the IBD Clinical and Research Centre would soon become a world leader in the investigation and management of inflammatory bowel disease, which is a term generally used to describe Crohn's and ulcerative colitis. That work would translate into leading-edge treatments for IBD, treatments that would help Harvie and others like him gain control over their conditions.

Today, the man who once couldn't leave his house for days at a time because he was too weak to get out of bed has reclaimed his life. With the symptoms of his disease largely in check for several years, Harvie, now 56, is finishing up a degree and leading a normal life, working as a vocation rehabilitation facilitator.

And, he says, he owes it all to Bernstein and his team at the IBD clinic. "I'm really lucky in a lot of respects that I live in Winnipeg," he says. "He (Bernstein) has basically given me my life back. I have a far better quality of life. That's not to say that I don't have a disability or there aren't some challenges, but they're much easier to accept."

Winnipeg did not become an international leader in IBD research overnight.

That process can be traced back to when Bernstein decided to continue his postgraduate training in Los Angeles. Initially, he thought he might specialize in liver disease. "When I went to UCLA to train, I thought I might actually become a liver doctor, but while I was there, they had a big IBD research program," Bernstein says.

By the early 1990s, he had completed his fellowship in gastroenterology. With a special interest in IBD and intestinal transplantation, he joined the Faculty of Medicine at UCLA.

He could have easily remained there and raised his family in Los Angeles with a comfortable, tenured career at the school as a specialist at one of the world's leading health-care centres.

But in 1993, Bernstein chose to return home to Winnipeg with his wife, Evelyn, to raise their two children, Matthew and Lexie, close to the rest of their family. His old hometown also offered something else: a chance to build a research and training program within the Section of Gastroenterology at the University of Manitoba's Faculty of Medicine. The IBD Clinic and Research Centre, located on the eighth floor of the John Buhler Research Centre at the U of M's Bannatyne Campus, was created soon after.

When Bernstein returned to Manitoba, gastroenterologists moving to the province were few and far between. "The last gastroenterologist to initiate a practice in Manitoba before me was in 1977," he says. In other words, there were thousands of Manitobans suffering from gastroenterological problems, the number of new cases of IBD was on the rise, and there was a dearth of expert care.

One of Bernstein's roles was to help develop the next generation of gastroenterologists in Manitoba, and by 1995, the Gastroenterology Fellowship Training Program at the U of M was up and running.

About 7,500 Manitobans have IBD. The condition is considered to be an autoimmune disorder (a condition that occurs when the body's immune system overreacts to substances and tissues normally present in the body) similar to rheumatoid arthritis or multiple sclerosis. But instead of attacking healthy joints, as is the case with arthritis, or the central nervous system in the case of MS, IBD attacks the digestive system.

When Bernstein was completing his fellowship in gastroenterology at UCLA 20 years ago, research into IBD had largely focused on looking at the immune system's response and how it caused IBD symptoms. The treatment focus was on dampening the response of the immune system.

But Bernstein planned to investigate the disease from a different perspective. "I thought we'd start by understanding what the population was who had IBD and work backward towards the individual from the population."

Bernstein wanted to understand what researchers call the "burden" of IBD in Manitoba. Data on how many people had it, what groups of people tended to get it, and trends in disease presentation and progression could ultimately lead to better management strategies.

As it turned out, Bernstein embarked on his ambitious goals at the right place at the right time. Dr. James Blanchard - a globally renowned epidemiologist - was leading the province's Epidemiology Unit at the time.

"I knew that we had tools in Manitoba that were quite unique through the administrative databases of Manitoba Health where every Manitoban has a unique personal health identification number so we could track their individual medical histories," Bernstein says.

Using the province's data, Bernstein worked with Blanchard to develop the University of Manitoba Inflammatory Bowel Disease Epidemiology Database. In doing so, they created the largest validated population database for IBD in North America, and one of only two on the continent (the other is at Mayo Clinic).

"This served as a fulcrum for developing our University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre here at the Health Sciences Centre," says Bernstein.

One of the major benefits of having these data at their fingertips was they could see the breadth of the disease amongst the population. "A main aspect of our research has been to define the epidemiology of inflammatory bowel disease locally, which means defining the burden of the disease, what type of people get this disease and how that's changed over time," he says. "We've been able to take the administrative definition of IBD we developed and apply it to databases elsewhere in the country to define the burden of disease across the country and show that Canada has amongst the highest rates of IBD in the world."

The database was the foundation for much of the research into IBD that would follow at the Centre for the better part of the next two decades. Bernstein and his team were able to look at who had the disease and identify what form of the disease they had. They could see when people were first presenting to the health-care system with symptoms, and they could also determine what type of other medical problems patients with IBD suffered from and how they were different than the general population. Furthermore, they could determine what type of treatment people were receiving and, to some extent, the effectiveness of those treatments.

Most importantly, the epidemiological information provided IBD researchers with a bird's-eye perspective of the illness. They could step back and observe that IBD was an auto-immune disease affecting about 500 people for every 100,000. They could also see that IBD rates were on the rise over the last five decades of the 20th century in the developed world, but much less prevalent in the developing world.

Beyond epidemiological studies, Bernstein and his team have initiated studies to explore potential causes of IBD, so that ultimately cures could be found. Their work has been highly cited and has had a major impact all over the world.

Simultaneously, Bernstein started a clinical trials program. "This provided Manitobans with IBD who were failing conventional therapy access to novel therapies," he says.

Bernstein says genetics play a large role in the causes of IBD. Some people are simply more prone to developing the disease. But as Bernstein and his colleagues continued to build upon epidemiological research, they also concluded that something in the environment was also playing a critical role.

One of the first indications of this reality came from studying first-generation Canadians whose parents immigrated to Canada from regions of low incidence. Children of these immigrants fell ill with IBD at the same rates as the rest of the Canadian population. Further, in the past 15 years IBD rates have been rising in the developing world - Asia, Africa and South America - too.

"So it begs the question: What has changed?" he says. "One hypothesis is that it is diet. That in the developing world, diets have become more westernized."

But demonstrating that rates were rising as a result of changes in our diet was one thing. Using that knowledge to pursue more effective treatments, and even possibly a cure, was another.

From the start, research into IBD at the centre branched out from epidemiological studies - understanding who had the disease - into many different fields of study. Clinical research, which aims to improve treatments, develop new drug therapies and promote overall care, has been especially important.

For Bernstein, that has meant working closely with patients. He estimates he spends about 60 per cent of his time in clinical practice. "Seeing patients provides us with research questions," he says. "It's also a connection to what's important to them and important in managing their disease."

But at the centre, they have also expanded their scope of study beyond the medical community to look at the possible environmental causes of IBD.

Bernstein has worked closely with Dr. Denis Krause, a professor in the Department of Agricultural Sciences at the U of M's Fort Garry campus, to investigate a possible environmental link between animal farming practices, food and water contamination with novel species of E. coli and other bacteria and IBD.

"Currently, a leading potential cause of IBD is that patients who are genetically predisposed to getting the disease react to something that is present within the bowel flora," Bernstein says.

The bowel flora refers to the ecosystem of bacteria that live within a bowel. These bacteria live within our digestive tract and help digest food, releasing nutrients that can be absorbed in the intestine.

The human gut contains billions upon billions of bacteria. "In fact, there are more bugs in our bowel than cells in our entire body," Bernstein says.

But he and Krause have determined that a certain type of E. coli is present in the gut of people who have IBD, a discovery supported by similar findings in seven other research labs around the world.

Many different strains of E. coli live within the digestive tract of different species of mammals and, in turn, are beneficial to the existence of those creatures. But some strains can be harmful. "Enterotoxigenic E. coli are a strain of E. coli that doesn't invade the cells in the gut, but instead releases a toxin," Bernstein says. "Those are the ones we think of when we go to Mexico and get turista (traveller's diarrhea)."

Other strains - like 0157:H7 - do invade the gut's lining and cause a hemorrhagic illness. "That is the E. coli of the outbreak in Walkerton, Ontario - that invades the gut and causes direct ulceration, and people get colitis and really sick," he says.

But IBD research here in Winnipeg and confirmed in other research centres found that both Crohn's disease and ulcerative colitis sufferers have an adherent-invasive strain of E. coli in their digestive tracts.

"We don't know that the E. coli is releasing any toxins, but we do know that it can stick to the gut and invade the epithelial (surface) cells so that's why it's been given this moniker of adherentinvasive."

Bernstein says a case control study found the bacteria were present in both people with IBD and those without. But the remarkable thing about the study is that it revealed that this strain of E. coli was present at greater rates and in greater quantities in individuals with IBD.

Bernstein says it's still too early to tell if this is the breakthrough discovery that will unlock the cause of IBD and ultimately lead to a cure, but it's an important first step; an important model of exploring the bowel flora of affected individuals. "In essence, it has unlocked a door that will advance our understanding of the human bowel providing the possible environmental link to this disease," says Bernstein.

This microscopic evidence - while potentially groundbreaking - is just one among many clues that Bernstein and other researchers are pursuing.

Research at the Centre approaches IBD from many different angles, bringing together experts from several medical and scientific disciplines. The more ways they can approach IBD from a research perspective, the more likely they'll be able to see "the big picture" and be able to put all the different key pieces of research together.

And each piece is important. Consider the work Bernstein is doing with Dr. Hani El-Gabalawy, an auto-immune diseases specialist. They are investigating why First Nations populations in Manitoba, who have high rates of gastroenterological problems and rheumatoid arthritis, have very low rates of IBD.

"Even though First Nations people get lots of GI symptoms, they don't get IBD, so they may hold a clue," Bernstein says. "It's as important to study a group that doesn't get IBD to understand the underpinnings of IBD as it is to study the group that does."

Other researchers at the Centre are studying the psycho-social component of the disease. Lesley Graff and John Walker, for example, are clinical health psychologists who have been involved in exploring the psycho-social aspects of gastrointestinal diseases, especially IBD.

Bernstein says that many sufferers of IBD, Harvie included, find that anxiety surrounding certain symptoms of the disease, such as incontinence, can make symptoms of the disease worse. Their research has shown that stress is associated with a flare of symptoms of IBD.

Bernstein says the research at the Centre, while expansive in scope, is all largely based on that epidemiological database developed nearly two decades ago. It is the framework from which all clinical investigations have flowed, leading to many groundbreaking discoveries, such as identifying the new E. coli strain. In turn, these findings have helped put the Centre - and Winnipeg - on the map in the global medical community.

And, in many instances, Bernstein has been the face of this collective research, representing the Centre, and appointed to leading positions at academic and clinical research organizations around the world.

He is the current Scientific Secretary of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD), which is an organization of 61 of the leading IBD investigators around the world. "Two years ago, we completed the University of Manitoba Bingham Chair in Gastroenterology," he says. "This is an endowment, and I am the inaugural Bingham Chair holder."

These appointments and accreditations do not simply represent widespread recognition by the medical community. They have also led to increased access to research funding. "The Bingham chair meant we had the funds to recruit Dr. Jean Eric Ghia, whose expertise is in studying the connection between the brain and the gut," says Bernstein.

While the Centre's prominence is no doubt a consequence of the good work being done here in Winnipeg, probably the biggest beneficiaries of all the research are the thousands of Manitobans suffering with IBD. Over the years, they have benefitted from enhanced care, including the opportunity to participate in the several drug trials carried out at the Centre.

Bernstein says patients at the Centre have been involved in the "seminal clinical trials" of both Remicade (infliximab) and Humira (adalimumab). These are among the latest pharmaceuticals currently available to patients suffering from a range of autoimmune disorders, including IBD. They belong to a class of drugs that cause the immune system to "down-regulate" or diminish its response to what it perceives as a threat to the body. This in turn alleviates the symptoms of diseases like IBD, which are largely caused by the immune system attacking healthy tissues in the body.

Harvie was one of the patients to benefit from participating in a drug trial at the centre. "John was enrolled in one of these early Humira trials," Bernstein says. "Not everyone responds to these drugs, but John responded very well and has remained on the drug after the study was completed and became available to the public."

Harvie says he had been involved in many trials at the centre, so many that Bernstein had often jokingly and endearingly referred to Harvie as his "professional study patient."

But Humira turned out to be the most successful. "My recovery has really been quite incredible," says Harvie.

Today, about 95 per cent of IBD sufferers can effectively manage their condition and lead full and productive lives. Still, Bernstein says drug therapies alleviating symptoms represent only one victory on the road to winning the war: finding the cure. "These are drugs that can cost $30,000 to $40,000 a year in any one individual, and in any one individual who is successfully treated with them, they often stay on these drugs for years," he says. "So, there are lots of economic considerations."

But up until research began at the Centre in the early 90s, a main effective treatment for IBD was surgery, removing the affected piece of the digestive tract. The procedure worked well for ulcerative colitis sufferers because their disease was localized to the colon.

"Obby Khan, the centre for the (Winnipeg) Blue Bombers, has promoted the notion that you can have a regular life with this, even more than a regular life" Bernstein says about Khan, who has been a patient of his after having such surgery. "He went back to playing professional football afterward, so you can live a normal life afterward."

But for Crohn's disease sufferers who may have disease in their small bowel and colon, surgery - while effective in some instances - may be a slippery slope.

"We're a little bit more circumspect about it because we're concerned that if we operate, the disease will occur again, and two, three or five years, we're back to square one, and we can't keep cutting."

Drug therapies hold the most hope for Crohn's sufferers like Harvie, who had part of his bowel removed before coming under the care of Bernstein. Yet a cure for IBD may not be that far away, Bernstein says, believing the mysteries of IBD will be unravelled in his lifetime. "I don't know if our group will be the ones to figure it out, but it will be figured out," he says.

Ultimately, he suspects it's likely there may be multiple causes to what may turn out to be multiple diseases. Yet, it is just as likely that one key discovery will unlock the secrets, much like in the case of peptic ulcers. They were once believed to be caused by over-production of stomach acid from stress and diet, until two Australian scientists discovered in the 1980s a type of bacteria, was the cause of these ulcers in up to 90 per cent of all cases. "When I was at UCLA, then a "mecca" for studying peptic ulcer disease, this organism - Helicobacter pylori - was just discovered and it changed the way we manage peptic ulcer disease," he says. "That is the Holy Grail: We're looking for that Helicobacter pylori equivalent in IBD."

Joel Schlesinger is a Winnipeg writer

About Wave

Wave is published six times a year by the Winnipeg Health Region in cooperation with the Winnipeg Free Press. It is available at newsstands, hospitals and clinics throughout Winnipeg, as well as McNally Robinson Books.

Bookmark Email Print Share this on Facebook SHARE Share this on Twitter Tweet RSS Feeds RSS
Make text smaller Make text bigger
Search this Site


Wait Times
View the current approximate wait times at Emergency Departments in the Winnipeg Health Region.

View wait times
Contact Us
Do you have any comments or concerns?

Click here to contact us
Find Services
Looking for health services in Winnipeg?

Call Health Links-Info Sante at 788-8200

Search the Health Services Directory

Explore alternatives to emergency departments at MyRightCare.ca

Find a Doctor
Wave Magazine
The Summer 2014 issue of Wave, Winnipeg's health and wellness magazine, is now available online.

Read more
eBulletin
Health Connection Winnipeg is your monthly electronic source for health related news and information from the Winnipeg Health Region.

Subscribe now
Careers
The Winnipeg Health Region has a variety of career opportunities to suit your unique goals and needs.

Visit our Careers site
WRHA Logo Help | Site Map | Terms of Use | Contact Us | En français