Conference Coverage

High stress linked to UC flare risk



– Early results from a cohort study that aims to characterize the brain-gut relationship in ulcerative colitis (UC) have identified potential structural and functional brain changes consistent with the effect chronic bowel inflammation has on the brain and found two subgroups of patients that differed in how they respond to stress. These findings may provide further insight into the role of the brain in symptom flares, the study leader reported the Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Dr. Emeran A. Mayer of University of California at Los Angeles Medical School

Dr. Emeran A. Mayer

So far, the study has shown that, based on validated measures of perceived stress or neuroticism, patients with UC in clinical remission are clustered on two ends of the stress spectrum, with high and low stress responsiveness, said Emeran A. Mayer, MD, who is coprincipal investigator of the study with Jenny Sauk, MD, both of the University of California, Los Angeles.

The goal of the longitudinal follow-up study is to identify brain, gut microbiome, and stress signatures that predict the risk of flares for up to 2 years in UC patients in clinical remission, he said. Patients’ clinical, microbiome, and stress-psychological measures are evaluated quarterly. The intent is to enroll 100- 120 patients between ages 18 years and 65 years. Questionnaire and symptom data on 70 patients have been analyzed so far.

“What we found so far is that, at baseline using the questionnaire data and clustering analysis, you can identify two distinct subgroups: one characterized by stress hyperresponsiveness and one that does not have that feature,” Dr. Mayer said in an interview. “Then we found in the stress hyperresponsive group there are more flares reported and documented during a mean follow-up of 8.1 months.”

The findings so far have also determined that the differences in stress responsiveness and flare frequency don’t seem to be related to baseline fecal calprotectin levels, said Dr. Mayer, who is director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience (CNSR) and codirector of the CURE: Digestive Diseases Research Center.

Early findings show the incidence of clinical flares in the high stress responsiveness group was 27.4% vs. 9.3% in the low-stress group, and the rate of symptomatic flares was 11.8% vs. 4.6%, respectively.

With regard to baseline biological measures, there were no significant differences in cardiovagal tone or morning salivary cortisol measures between the two clusters, Dr. Mayer noted, although the high stress responsiveness cluster had higher sympathetic tone before, during, and after a brief psychological stress.

He noted that the same clustering into low and high stress responsiveness was confirmed in a different data set of 66 UC subjects and that the two clusters showed significant differences in anatomical connectivity of the default mode network in the brain, a set of regions involved in chronic pain and emotion regulation.

By identifying factors that contribute to inflammatory bowel disease, the study may ultimately simplify the process of identifying IBD patients in remission who are at highest risk of flares, Dr. Mayer said. “Patients won’t need to undergo brain imaging or assessment of microbiome parameters; they can just answer a short questionnaire,” he said. Another potential benefit of the study would be to identify changes in the brain–gut microbiome interactions associated with flares, he said.

Full study results would be available in about 2 years, Dr. Mayer said, with more data on biological parameters expected next year.

The study is funded with a Crohn’s & Colitis Foundation grant. Dr. Mayer disclosed financial relationships with Amare, Axial Biotherapeutics, Bloom Science, Danone, Mahana Therapeutics, Pendulum, Ubiome, and Viome.

SOURCE: Mayer EA et al. Crohn’s & Colitis Congress 2020, Session Sp74.

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