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the future of crohn's disease: breakthrough research reveals cause and new treatment options

the genetic, environmental and microbial (gem) project, launched in 2008 by crohn’s and colitis canada and its research partners, has revealed that years before the development of crohn’s disease, the gut bacteria of those who go on to develop it is different from those who remain healthy.

crohn's disease research unlocks cause and treatment options
angela faber, left, watched her sister jessica mccloskey, right, struggle with crohn's disease symptoms for years until she was finally diagnosed. supplied
angela faber says it’s been tough to watch her little sister struggle with health problems through her high school years and into adulthood when her symptoms of severe abdominal pain and frequent diarrhea got worse.
“she had the runs all the time, but we don’t really talk about that stuff. it wasn’t that bad when she was younger, but as life progressed and stresses came on being a mom, working and trying to hold a household together, she really had a hard time. and she was sick as a dog the whole way through her pregnancy,” said faber, who lives in victoria, b.c.

faber’s sister in nearby nanaimo, jessica mccloskey, was diagnosed with crohn ’s disease soon after she had her son, who is now 19, finally putting a label on her debilitating symptoms and moving her forward to treatment.

identifying symptoms and diagnosing crohn’s disease

crohn’s disease and ulcerative colitis are the two main forms of inflammatory bowel disease (ibd) , a lifelong autoimmune condition where your immune system mistakenly attacks the lining of your gastrointestinal (gi) tract and interferes with your ability to digest food, absorb nutrients and excrete waste in a healthy way. crohn’s can strike anywhere from mouth to anus, but it’s usually located in the lower part of the small bowel or the colon.

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signs to watch for include diarrhea, constipation, rectal bleeding, blood in stool, weight loss, joint pain and fatigue, according to crohn’s and colitis canada . people can experience periods of acute symptom flare ups and also periods when symptoms go into remission – but there is no cure.

“once she was diagnosed, then it gave us an ‘aha, that’s what it is’ explanation,” faber said, adding her sister had surgery to remove part of her small intestine and has been hospitalized over the years because of pain and inflammation. different medications have helped, along with avoiding her “trigger foods” like beef and anything with skins or seeds, including grapes and tomatoes, or grain breads that she can’t digest and feel like gravel in her gut.
“she’s really, really struggled,” faber added. “you can’t do what you want when you want because you have to know where a bathroom is. you have to know your escape route, basically.”

while the exact cause of the disease isn’t known, factors have been linked to the environment and the gut microbiome, and a genetic predisposition, so people with family members with the disease are at greater risk. and the prevalence is rising, with 322,600 canadians estimated to be living with ibd in 2023 and a jump to 470,000 expected by 2035 (1.1 per cent of the population). crohn’s and colitis canada recently issued the 2023 impact of inflammatory bowel disease in canada report to flag the rapidly increasing number of people with ibd and improve access to care.

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the genetic, environmental, and microbial (gem) project: uncovering new paths in crohn’s disease research

now faber’s love and concern for her little sister have helped move the crohn’s and colitis research community to breakthrough findings that experts say will improve treatment and even prevent crohn’s disease. faber is one of the healthy relatives of people with crohn’s disease around the world who have participated in a unique international study headed by a canadian team.

the genetic, environmental and microbial (gem) project , launched in 2008 by crohn’s and colitis canada and its research partners, has revealed that years before the development of crohn’s disease, the gut bacteria of those who go on to develop it is different from those who remain healthy.

gastroenterologist dr. ken croitoru of mount sinai hospital in toronto , part of sinai health, is the gem project architect and lead investigator on the study. he says the discovery of a pattern of gut bacteria as a trigger for crohn’s disease will benefit patients through specific treatments focused on the gut bacteria or diet modification that affects the gut.

“this is really the absolute first step to moving towards improving our treatment and possibly even finding a cure,” croitoru said.

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“some patients have a very difficult time requiring multiple surgeries and have a life with chronic pain and chronic diarrhea. our current therapies, which are major advances, still only treat about 50 per cent of our patients,” he added. “when they work, they work great. when they don’t, it unfortunately can be very difficult. the main challenge is we still need to be able to improve our treatment, which is only going to come through better understanding of the actual underlying mechanisms. and i think that’s the future here. i see [the gem results] as a major step forward.”
 “when you’re trying to focus on the inflammation, that fire has already started and we’re trying to put it out,” gastroenterologist dr. ken croitoru (pictured) of mount sinai hospital in toronto said. “so you have to get at the root of why the fire started.”
“when you’re trying to focus on the inflammation, that fire has already started and we’re trying to put it out,” gastroenterologist dr. ken croitoru (pictured) of mount sinai hospital in toronto said. “so you have to get at the root of why the fire started.” sinai health
the mount sinai team, in collaboration with researchers in the u.s., the u.k., israel, australia, new zealand and sweden, recruited 5,000 healthy children and siblings, like faber, of people with crohn’s disease over the past 15 years to look at their diet, immune function, intestinal barrier, gut bacteria, genetics and environment. after initial testing, participants were followed with a check-in every six months to see if they developed crohn’s disease.
more than 100 participants have developed crohn’s, allowing for a comparison of the initial samples taken when those participants were healthy with initial samples taken from participants who did not develop the disease. croitoru says the study design, called a prospective cohort study, provides an ideal window for scientists to examine what is different about those samples and determine possible disease triggers and development.

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he also explains that microbiome analysis, which has been done many times in a case control study where people with disease are compared to healthy participants, is challenging because there are so many things that will confound the outcome. whether participants are taking medications or antibiotics or even the actual disease itself, the inflammation that comes with crohn’s will alter the gut bacteria of the microbiome.
“when you’re trying to focus on the inflammation, that fire has already started and we’re trying to put it out,” he said. “so you have to get at the root of why the fire started.”

the complex nature of crohn’s disease and the role of gut bacteria

another challenge for researchers is the complexity of crohn’s when it comes to identifying the gut bacteria and mechanisms behind the disease. by contrast, if you look at an infection like pneumonia, you can find this single bacteria that is responsible for that pneumonia, and you can give an antibiotic, get rid of that bacteria and cure the pneumonia.

complex chronic diseases like crohn’s disease, can’t be traced to a single bacteria. bbc science describes the human gut microbiome as where “thousands of native bacteria live in partnership with us. they survive a hostile environment of darkness, high acidity and low oxygen, in what is a tumultuous river flushing through the stomach and intestines.”

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croitoru explains that while gem has determined that the community of bacteria in the gut is changed years before the onset of crohn’s, because bacteria serve many functions in the gut, what comes next is looking at those functions and their interaction with the immune system to drill down to specific disease triggers.
“we have found a number of changes in the types of bacteria. we have also found a number of changes in what these bacteria can do, what their genetic capability is, what they may produce in terms of enzymes or metabolites, all of which can affect the person’s gut function, and more importantly, can influence gut inflammation,” he confirmed.
“so this is the first step of trying to understand what might be a trigger for crohn’s disease that is focused on understanding the gut bacteria and how it interacts with the person.”
the aim is to continue the gem project investigation, looking at the ability of the gut to digest certain food products in the intestine, for example, and then develop diet therapy for prevention and treatment.
faber will definitely continue with the study. “this is so much bigger than i thought it was at the very beginning. i didn’t realize how significant it is and that they’ve started to find some answers at least as to why it’s happening. it’s amazing.”

raising awareness and understanding the signs of crohn’s disease

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while it’s a possibility that her kids, now 21 and 16, could have inherited crohn’s, faber says she’s been on alert since her sister’s diagnosis and talks about possible symptoms with her kids to raise their awareness as well. “there have been many discussions about poop.”
she doesn’t know of anyone else in the family besides her younger sister who has crohn’s. however, she says that every family member has some kind of autoimmune deficiency. faber has allergies, her son has skin issues, her brother has asthma and alopecia universalis, a condition that leads to complete loss of hair on your scalp and body.
“i think that the more knowledge we have about crohn’s, and the sooner you can modify what you need to modify instead of having to take medication, that’s always better,” she said.
“i know how debilitating it can be, and especially at the beginning when it’s undiagnosed. if you have concerns about your gut and what’s going on in the bathroom, then you should get checked because there is help and there are studies like this one that are making remarkable discoveries.”
karen hawthorne is a toronto-based writer.
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karen hawthorne
karen hawthorne

karen hawthorne worked for six years as a digital editor for the national post, contributing articles on health, business, culture and travel for affiliated newspapers across canada. she now writes from her home office in toronto as a freelancer, and takes breaks to bounce with her son on the backyard trampoline and walk bingo, her bull terrier.

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