IBD and Environmental Triggers
We know that the environment plays a major role in triggering the onset of IBD and in causing relapses.
Understanding how environmental factors exert these effects could open up different research approaches that might lead to new types of treatment options and possibly even help prevent IBD.
Currently, we’re funding research to explain the role of the following environmental factors:
Diet
The Foundation has understood for many years that diet, nutrition and the microbiome collectively play an important role in IBD. For a summary of what is known today about diet and nutrition for IBD, please click here.
In 2021, the Diet to INducE Remission in Crohn’s Disease (DINE-CD) study, which was supported by the Foundation, was published, the first-ever study to compare the Specific Carbohydrate Diet™ to a Mediterranean-style diet to manage Crohn’s disease symptoms. In the study, patients were randomly assigned to follow one of the two diets. About half of participants in both groups saw an improvement in symptoms, demonstrating that diet may have an impact on IBD symptoms.
We are now aiming to take diet research a step further with our Precision Nutrition Initiative, which is generously supported by Jonathan D. Rose, MD, PhD.
This ongoing program is delving into the fields of nutrigenomics (the interplay of nutrition and your genes), metabolomics (how your unique metabolic profile affects your health), and microbiomics (how your unique gut microbial profile affects your health).
Scientists already suspect that many patients have unique biological characteristics that cause their body to ramp up inflammation or calm it down when they eat certain foods. However, they're still sorting out which foods do what in each of us.
Meanwhile, scientists are looking to identify biomarkers—measurable indicators that can be detected in blood or other body fluids or tissues—that can one day be used to predict how a given IBD patient would respond to a specific diet. If we can pinpoint the connection between specific biomarkers and foods, patients might one day be able to take a simple blood test and quickly learn which foods to avoid or eat more of.
The following four projects were selected for our Precision Nutrition initiative. We believe that by investing in these programs we will move closer to the ultimate goal of providing evidence-based, personalized nutrition recommendations for everyone with IBD.
Using Artificial Intelligence to Predict Response to Diet
Why can one person with IBD enjoy a certain food while another finds that the same food sends them into a flare? Thanks to a research grant from our Precision Nutrition initiative, researchers at the University of California, San Diego hope to find out.
The researchers are now creating a "food-specific metabolomic signature" for thousands of popular foods. Essentially, they're describing foods based on the metabolic end products that result in the body after someone eats them. Using a grant from the Precision Nutrition Initiative, they will next attempt to use artificial intelligence to determine what someone ate simply by analyzing a sample of their blood, urine, or stool. In other words, they'll be able to tell what someone ate without even asking them. This is important because food diaries are often unreliable and difficult to maintain.
The research team is hoping to prove that this is possible and that they can use this methodology to show not only which foods someone has consumed but also which non-food substances, such as pesticides, might have been ingested in the process.
As part of this project, the same researchers will be analyzing the microbiomes (bacteria and other microbes in the gut) of participants to see whether differences in their composition alter how end products known as food metabolites impact disease activity and progression.
Matching Patients to an Anti-Inflammatory Diet
Although medication remains crucial, many patients with Crohn's disease hope to supplement their treatment with dietary changes. Preliminary research supports the notion that red meat, food additives, and preservatives may be detrimental to people with IBD. It also suggests that increased intake of antioxidant-rich fruits and vegetables, resistant starch (found in certain grains and legumes), and fatty fish like salmon and mackerel all help to reduce symptoms—at least in certain patients.
Researchers at the University of Calgary are using a grant from the Foundation’s Precision Nutrition Initiative to identify a "multi-component signature" that might one day be used to predict which patients can quickly reach remission with the help of a specific anti-inflammatory diet. The goal: to figure out which patients respond to this diet based on their unique biochemistry and convert the data they gather on each patient into a combined score that takes a person’s genetics, microbiome composition, and metabolism into account.
Determining Which Foods Keep Teens in Remission
Although it’s not popular in the U.S., enteral nutrition—a formula-based liquid diet that’s sometimes administered via a feeding tube—is a well-established treatment for mild Crohn's disease. Many pediatric and adolescent patients are able to reach remission after about 8 weeks on such a diet, but during that time they don’t eat any regular food.
Few people want to stay on an exclusive, formula-based liquid diet forever. Researchers at the University of Glasgow want to find out why and what to do about it. They believe they can tip the odds in a patient's favor by having them follow a plan called CD-TREAT. They've already published a preliminary study in the journal Gastroenterology, which found that IBD patients who stick to CD-TREAT—a solid food diet that mimics key characteristics of the liquid diet by limiting gluten, fiber, and food additives—have lower levels of gut inflammation and reduced disease activity.
Using a grant from the Foundation’s Precision Nutrition initiative, they will now aim to identify the dietary triggers of relapse after patients on a liquid plan return to normal food. They also aim to determine whether teenagers who go on CD-TREAT immediately after achieving remission on a liquid diet will fare better than those who resume their normal eating habits. Study participants are randomly assigned to a group and asked to keep food diaries for 21 days. Researchers are also collecting blood and stool samples so they can attempt to measure immunological and microbiological biomarkers related to the consumption of specific foods.
Enrollment in the UK and Scotland is now ongoing.
Determining Who Benefits Most from Avoiding Processed Foods
Whole foods are healthy for everyone, but are highly processed ones especially damaging for certain IBD patients? Researchers at the University of California, Los Angeles plan to use a combination of biological data to identify signatures that may be used to predict who is most apt to reach remission by following a whole foods diet while staying on current medications.
The research team will run a randomized clinical trial including more than 100 people with mild to moderate Crohn's disease. One group will follow their usual diet; the other will follow a carefully orchestrated whole foods diet. Both groups will continue taking their usual medications.
The scientists will also be analyzing the micro-RNA of participants, which are tiny pieces of genetic material that turn genes on and off. The goal is in the near future to be able to use information about someone’s micro-RNA profile to match them to a diet that will elicit the best response.
Patients interested in enrolling in this Los Angeles, CA-based study can learn more here.
Stress
Research suggests that people with IBD often experience anxiety and depression in response to exposure to psychological stress, but exactly how stress relates to symptoms, disease progression, and relapse has been unclear. Research funded by the Foundation now reveals a direct connection.
Scientists at the David Geffen School of Medicine at the University of California Los Angeles and UCLA’s G. Oppenheimer Center for Neurobiology of Stress and Resilience have already learned that some ulcerative colitis patients who display high levels of stress and anxiety are significantly more likely to experience flares. To reach that conclusion, study participants were given brain imaging tests, behavioral assessments, and a special skin test (Electrodermal activity, or EDA) that provides an objective measurement of stress at the time of enrollment and at three-month intervals for the duration of the study.
In another study, scientists at the University of Alabama at Birmingham are making progress in identifying mechanistic pathways sensitive to early life stress (ELS) leading to high risk of IBD progression and relapse. Understanding the basic mechanisms by which one responds and adapts to psychological stress in early life will lay the foundation for learning about how stress and the bidirectional gut-brain communication regulates the inflammatory response in the pediatric population.
In preclinical studies, researchers found that ELS decreased the diversity of microbes in the gut of four-week-old mice. This is an important finding, since decreased diversity is linked to IBD in humans. In particular, they found a decrease in the bacteria that produce short chain fatty acids (SCFA) like butyrate, which are microbial products necessary for the maintenance of the intestinal wall integrity and health. These results indicate that ELS alters the gut microbial ecosystem by depleting beneficial bacterial populations and offers novel readouts to be evaluated in IBD patients exposed to ELS. These findings were reported in a peer reviewed publication.
The University of Alabama researchers are also evaluating the role of ELS on exacerbation of colonic inflammation in animal models of IBD, the specific immunological and biochemical mechanisms that may be involved and the identification of potential therapeutic targets. Importantly, the effects of ELS on IBD disease progression and relapse are also being evaluated in a group of adolescents being followed as part of this research study. Biochemical, immunological, and microbiological parameters are also being studied in this group to identify mechanisms and potential biomarkers of ELS exposures and whether they can be used to predict stress reactivity and its effects on disease progression.
These investigations could lead to the design of diagnostics for childhood stress for IBD risk, as well as prevention strategies and therapies for the management of stress-related disease relapses.
