Study: CBT Alters Brain-Gut Microbiome in IBS Patients

The study, titled “Cognitive Behavioral Therapy for Irritable Bowel Syndrome Induces Bidirectional Alterations in the Brain-Gut-Microbiome Axis Associated With Gastrointestinal Symptom Improvement,” was published Nov. 30 in the journal Microbiome.

It is the first to show how cognitive behavioral therapy can teach patients information processing skills that address the biological roots of their GI (gastrointestinal) symptoms.

“This work demonstrates that teaching people how to think more flexibly in specific situations can reduce the physical tension and stress that can disrupt brain-gut interactions and crank up symptoms,” says Jeffrey M. Lackner, PsyD, co-senior author on the paper, professor in the Department of Medicine and chief of its Division of Behavioral Medicine.

The study, conceived by an interdisciplinary UB team, shows how a non-drug, non-dietary treatment for IBS induces changes in brain function and in the microbiome by normalizing ways of processing information, Lackner explains.

“These results will have a dramatic impact on understanding a gastrointestinal disease that has a significant public health burden,” he says.

“Dr. Lackner’s collaborative project with UCLA is an important breakthrough in the understanding of how cognitive behavioral therapy can alter brain-gut interaction to provide relief for IBS patients,” says Allison Brashear, MD, UB’s vice president for health sciences and dean of the Jacobs School of Medicine and Biomedical Sciences. “This study’s translational research provides new hope for those afflicted with this debilitating disease.”

“The findings are the first to demonstrate that a specific type of cognitive behavioral therapy developed at UB that teaches information processing skills can modulate key components of the brain-gut-microbiome axis in some of the most severe IBS patients,” Lackner says.

“We know that the gut microbiome is key to regulating brain-gut interactions and plays in overall human health from metabolism to immunity. We also know learning-based treatments like cognitive behavioral therapy are some of the most robust treatments of any kind for what IBS is — the most prevalent GI disease — even when they are delivered with minimal doctor involvement,” he adds.

“What we don’t know is how those two facts interact. We don’t know whether symptom relief following CBT depends on the microbiome environment to achieve its effects.”

“This study is important because it shows that we see a precise microbiome signature that distinguishes patients who respond positively to a drug-free treatment and those who don’t, and that signature corresponds with objective changes in brain function,” Lackner says.

“The fact that we see patient-reported GI symptom improvement that correspond with ‘objective’ biological changes in the microbiome and brain function is pretty remarkable given that we focused on a low-intensity behavioral treatment and not medical therapies like probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation known to manipulate our microbiome,” Lackner says.

“This is paradigm shifting for how we understand the role of the microbiome and therapeutics that can modify its composition to treat and prevent disease.” 

Eighty-four IBS patients were recruited from the parent CBT trial — the Irritable Bowel Syndrome Outcome Study, a landmark, National Institutes of Health-funded clinical trial led by Lackner that has transformed the way IBS is understood and treated.

The 84 participants underwent neuroimaging and detailed clinical assessment at clinical sites a UB and Northwestern University. UB also collected microbiome data through fecal sampling from 34 of the patients.

Eligible patients were randomized to receive 10 sessions of clinic-based CBT or four sessions of largely home-based CBT with minimal therapist contact over a 10-week acute phase. Both treatments were developed at UB.

“This trial was enormously complex in that we collected symptom data across different sites at pre-treatment and post-treatment,” says Lackner, who sees patients at the Behavioral Medicine Clinic at UBMD Internal Medicine. “Because we were also collecting biological data at multiple times, it required a high level of precision and project management unique among major research centers. It really speaks to our division’s capacity to support boundary-breaking, novel translational research with high impact potential.”

UB partnered with the David Geffen School of Medicine at UCLA, and the G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA.

“All that data had to be expertly analyzed and that is where we were able to draw from the expertise of our longstanding collaborators at UCLA, experts in microbiome and imaging research” Lackner says.

UB developed the treatment, delivered it and collected data while UCLA analyzed gut microbiome and neuroimaging data. Both teams collaborated on preparation of the manuscript.

Emeran A. Mayer, MD, an internationally known expert on the interactions between the digestive and nervous systems, is co-senior author on the paper. He is a professor in the David Geffen School of Medicine at UCLA and executive director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience.

“It is a great example of team science between two outstanding research facilities with unique synergies,” Lackner says. “There’s a lot of reasons why this type of study hasn’t been done up to now, but we were able to leverage our unique clinical expertise and our clinical research infrastructure and UCLA’s expertise.”

Of the 84 participants in the trial, 58 were classified as CBT responders and 26 were classified as non-responders.

While there were small pre-treatment differences between brain network connectivity for responders and non-responders, the significant difference was how much the connectivity changed after treatment.

Responders showed greater baseline connectivity than non-responders between the central autonomic network and the emotional regulation network, according to the study.

A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy, raising the possibility that CBT-responsive IBS patients can be identified in clinical practice using microbial biomarkers, Lackner says, before less effective treatments are initiated at great expense to the patient and health care system.

“The pattern of data may explain normal versus abnormal gut function and just how the brain-gut can influence symptoms and the relief of them,” Lackner says. “Larger studies are needed to characterize the functional correlates of gut microbial changes and to identify distinct subtypes of IBS patients for whom brain- and gut-directed therapies are most effective.”

“This is an example of science moving away from ‘one size fits all’ brand of medicine toward a more personalized medicine approach driven by translational research.”

Jonathan P. Jacobs, MD, PhD, and Arpana (Annie) Gupta, PhD, both of the David Geffen School of Medicine at UCLA, and the G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, are the study’s co-first authors.

Co-authors from the Jacobs School’s Division of Behavioral Medicine are:

• Rebecca S. Firth, division administrator and research coordinator
• Gregory D. Gudleski, PhD, research assistant professor

Other co-authors are from the following institutions:

• David Geffen School of Medicine at UCLA
• G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA
• Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine at University of Southern California

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases to Lackner and Mayer, UB’s Office of the Vice President for Research and Economic Development and UB’s Genome, Environment and Microbiome (GEM) Community of Excellence.