Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement

Microbiome

Benjamin M. Ellingson¹  Venu Lagishetty²  Rebecca Firth³  Gregory D. Gudleski³  Jeffrey M. Lackner³  Kan Gao⁴  Jacob Brawer⁴  Kirsten Tillisch⁴  Arpana Gupta⁴  Jennifer S. Labus⁴  Bruce D. Naliboff⁴  Jonathan P. Jacobs⁵  Emeran A. Mayer⁶  Ravi R. Bhatt⁷ 

[1]David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

[2]Department of Radiological Sciences, UCLA, Los Angeles, CA, USA

[3]Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA

[4]David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

[5]Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA

[6]Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA

[7]Division of Behavioral Medicine, Jacobs School of Medicine, University at Buffalo, SUNY, Buffalo, NY, USA

[8]G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA

[9]David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

[10]Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA

[11]G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA

[12]David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

[13]Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA

[14]Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA

[15]G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA

[16]David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

[17]Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA

[18]G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David School of Medicine at UCLA, CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, USA

[19]Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine at USC, University of Southern California, Los Angeles, USA

关键词: Cognitive behavioral therapy;    Irritable bowel syndrome;    Brain-gut-microbiome axis;    Neuroimaging;    Biomarkers;    Outcome prediction;   

DOI  :  10.1186/s40168-021-01188-6

来源: Springer

【 摘 要 】

BackgroundThere is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis.MethodsEighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models.ResultsAt baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders.ConclusionsPre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT.8UBWhk6mapSqW3WwW-uhWTVideo abstract

【 授权许可】

CC BY