Foundation Research Sheds Light on Stress-Induced Ulcerative Colitis Flares

If you have ever said, “I have a gut feeling” or “my gut tells me,” you have acknowledged the connection between the gut and the brain. But as common as these phrases may be, there are still many unanswered questions about how the gut and brain relate to one another.

The Crohn’s & Colitis Foundation launched a patient-centric Environmental Triggers research initiative in 2016 with the clear vision to better understand how exposure to environmental factors, including stress and diet, can affect Crohn’s disease or ulcerative colitis onset, progression, or relapse. The initiative also hopes to identify the biological changes driving these effects. The Foundation attracted prominent researchers to accomplish this goal, who recently reported the identification of biomarkers that predict which ulcerative colitis patients will experience a flare in response to high levels of stress.¹

The research study, conducted by Dr. Emeran A. Mayer, MD, and colleagues at the University of California, included 91 patients with ulcerative colitis; these patients were grouped into a high stress reactivity (SR) group and a low SR group based on their answers to a questionnaire.^1,2

At the start, all participating patients were in clinical and biochemical remission, meaning that not only were they symptom-free, but laboratory results indicated that they had no signs of active disease. In addition to their stress reactivity, each participant had their fecal microbe, fecal metabolite, and plasma metabolite profiles analyzed.¹
 

The researchers concluded that certain microbial signatures are associated with high SR and high clinical flare risk. This finding indicates that an ulcerative colitis patient’s microbiome may contribute to stress-induced flares of their disease.¹

Participants with higher SR shared several characteristics of their fecal microbes, including an abundance of the Ruminococcaceae and Lachnospiraceae families, as well as shared signatures in their fecal metabolite and plasma metabolite results. These signatures were proven to accurately predict patients’ risk for clinical flares.¹

While intestinal inflammation due to a clinical flare did not change participants’ fecal microbe abundances, it did reduce the differences in fecal metabolite and plasma metabolite markers between the low SR group and the high SR group.¹

Implications for the Future of IBD Care

Now that it is known that patients with high SR can be distinguished from patients with low SR via their fecal microbe, fecal metabolite, and plasma metabolite profiles, a potential prognostic test could be developed to determine which patients are at greatest risk of experiencing a stress-induced flare.¹

In addition to identifying candidate biomarkers that can indicate which patients would benefit most from access to stress management interventions to prevent flares, this study also identified pathways between the gut and the brain that are related to stress. In the future, these stress-related pathways could become therapeutic targets, expanding treatment options for patients.¹

1. Jacobs JP, Sauk JS, Ahdoot AI, Liang F, Katzka W, Ryu HJ, Khandadash A, Lagishetty V, Labus JS, Naliboff BD, Mayer EA. Microbial and Metabolite Signatures of Stress Reactivity in Ulcerative Colitis Patients in Clinical Remission Predict Clinical Flare Risk. Inflamm Bowel Dis. 2023 Aug 31:izad185. doi: 10.1093/ibd/izad185. Epub ahead of print. PMID: 37650887.
2. Sauk JS, Ryu HJ, Labus JS, Khandadash A, Ahdoot AI, Lagishetty V, Katzka W, Wang H, Naliboff B, Jacobs JP, Mayer EA. High Perceived Stress Is Associated With Increased Risk of Ulcerative Colitis Clinical Flares. Clin Gastroenterol Hepatol. 2023 Mar;21(3):741-749.e3. doi: 10.1016/j.cgh.2022.07.025. Epub 2022 Aug 8. PMID: 35952942.

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