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Physiological Stress Measures Predict Ulcerative Colitis Flares

— Unpacking the link between the brain and the microbiome

Last Updated January 27, 2020
MedpageToday

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AUSTIN -- Patients with higher levels of stress reactivity had more frequent ulcerative colitis flares, according to a small study presented here.

Among 93 patients with ulcerative colitis in symptomatic remission, those with higher levels of stress reactivity -- a composite measure of perceived stress and trait anxiety at baseline -- were significantly more likely to experience clinical flares across 8 months (27.4% vs 9.3%, P=0.03), reported Jenny Sauk, MD, of the David Geffen School of Medicine at the University of California Los Angeles (UCLA).

Notably, between patients with high versus lower levels of stress reactivity, there was no difference in baseline fecal calprotectin, a measure of disease activity, Sauk said during a poster presentation at the Crohn's & Colitis Congress.

"You would think patients who are going to flair more will have higher calprotectin at baseline because calprotectin is a marker of inflammation," Sauk told 鶹ý. "At baseline, the [calprotectin levels] were not higher, but these patients are still reporting more clinical flairs, so it doesn't seem to be correlated with our objective measure of inflammation."

Although anxiety and depression have been shown to with irritable bowel disease (IBD), the role stress plays on IBD symptoms remains unclear, said co-author Emeran Mayer, MD, also at UCLA, during a presentation on the gut-brain connection.

However, stress has been shown to have effects on mucus, permeability, and immune function in murine models, he noted. It may also play a role in noradrenergic signaling and other microbiota processes.

"Based on this study, you can see that ulcerative colitis patients in clinical remission show structural and functional brain changes consistent with the effect of chronic gut inflammation on the brain," Mayer said.

The study involved 93 adult patients with Simple Colitis Clinical Activity Index (SCCAI) scores under 5, indicating they were in symptomatic remission. Sauk and colleagues performed brain imaging, behavioral assessments, and autonomous nervous testing (ANT) involving arithmetic stress testing at baseline. Patients were then assessed for changes in stress reactivity every 3 months and at the time of flares.

In the cohort (median age 35; 48% female; median BMI 23.5) 30% had extensive ulcerative colitis, 41% had left-sided ulcerative colitis, and 17% had ulcerative proctitis. The group had been diagnosed a median 8.4 years prior. Also, 74.2% were on mesalamines, 13.9% were on thiopurines, and 24% were on anti-tumour necrosis factor (TNF) agents.

Sauk and colleagues also measured "subjective" flares by asking patients if they thought they were in a flare to determine if this measure was associated with flares.

However, only the clinical flares measured through SCCAI scores -- and not the subjective flares -- were significantly associated with stress reactivity, Sauk said. In total, 18 clinical flares and eight symptomatic flares occurred.

Moreover, vagal tone, measured through heart rate variability, did not significantly change among participants across the study, Sauk reported.

"That's important because there are some theories out there that suggest more sympathetic activation could be associated with inflammation," Sauk said.

This study is ongoing, and Sauk's group is also collecting brain MRI imaging and microbiome data. She said she hopes research into stress-related physiological measures can inform future research into interventions like mindfulness and meditation.

"[Patients] really do feel stress makes them feel worse, and if we can say this is true, and if their symptoms respond to stress reduction, that's a win," Sauk said.

  • author['full_name']

    Elizabeth Hlavinka covers clinical news, features, and investigative pieces for 鶹ý. She also produces episodes for the Anamnesis podcast.

Disclosures

The study was funded by the Crohn's and Colitis Foundation and the NIH.

Sauk disclosed no relevant relationships with industry.

Mayer disclosed relevant relationshiops with Danone, Viome, Amare, Axial Biotherapeutics, Pendulum, uBiome, Bloom Science, Mahana Therapeutics, and APC Microbiome Ireland.

Primary Source

Crohn's & Colitis Congress

Sauk J, et al "High stress reactivity and increased symptom flares in ulcerative colitis patients" CCC 2020.

Secondary Source

Crohn's & Colitis Congress

Mayer EA, et al "Understanding the language of the gut-brain dialogue: Implications for IBD" CCC 2020.