Display options
Cite
Jacobs JP, Gupta A, Bhatt RR, et al. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome. 2021;9(1):236doi: 10.1186/s40168-021-01188-6.
Jacobs, J. P., Gupta, A., Bhatt, R. R., Brawer, J., Gao, K., Tillisch, K., Lagishetty, V., Firth, R., Gudleski, G. D., Ellingson, B. M., Labus, J. S., Naliboff, B. D., Lackner, J. M., & Mayer, E. A. (2021). Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome, 9(1), 236. https://doi.org/10.1186/s40168-021-01188-6
Jacobs, Jonathan P, et al. "Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement." Microbiome vol. 9,1 (2021): 236. doi: https://doi.org/10.1186/s40168-021-01188-6
Jacobs JP, Gupta A, Bhatt RR, Brawer J, Gao K, Tillisch K, Lagishetty V, Firth R, Gudleski GD, Ellingson BM, Labus JS, Naliboff BD, Lackner JM, Mayer EA. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome. 2021 Nov 30;9(1):236. doi: 10.1186/s40168-021-01188-6. PMID: 34847963; PMCID: PMC8630837.
Copy Download .nbib Format: NLM
Share it on

Microbiome. 2021 Nov 30;9(1):236. doi: 10.1186/s40168-021-01188-6.

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

Microbiome

Jonathan P Jacobs, Arpana Gupta, Ravi R Bhatt, Jacob Brawer, Kan Gao, Kirsten Tillisch, Venu Lagishetty, Rebecca Firth, Gregory D Gudleski, Benjamin M Ellingson, Jennifer S Labus, Bruce D Naliboff, Jeffrey M Lackner, Emeran A Mayer

Affiliations

  1. G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.
  2. David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  3. Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
  4. Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
  5. 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.
  6. Division of Behavioral Medicine, Jacobs School of Medicine, University at Buffalo, SUNY, Buffalo, NY, USA.
  7. Department of Radiological Sciences, UCLA, Los Angeles, CA, USA.
  8. Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA.
  9. G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA. [email protected].
  10. David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. [email protected].
  11. Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA. [email protected].
  12. 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. [email protected].

PMID: 34847963 PMCID: PMC8630837 DOI: 10.1186/s40168-021-01188-6

Abstract

BACKGROUND: There 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.

METHODS: Eighty-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.

RESULTS: At 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.

CONCLUSIONS: Pre-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. Video abstract.

© 2021. The Author(s).

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

References

  1. Gastroenterology. 2009 Dec;137(6):1944-53.e1-3 - PubMed
  2. Genome Biol. 2014;15(12):550 - PubMed
  3. Pain. 2013 Oct;154(10):2088-2099 - PubMed
  4. Gastroenterology. 2018 Oct;155(4):960-962 - PubMed
  5. Gastroenterology. 2018 Jul;155(1):47-57 - PubMed
  6. Cell Mol Gastroenterol Hepatol. 2016 Jul 02;2(6):750-766 - PubMed
  7. Gut. 2019 Sep;68(9):1701-1715 - PubMed
  8. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402 - PubMed
  9. Pain. 2013 Sep;154(9):1528-1541 - PubMed
  10. Neuroimage Clin. 2014 Jul 23;5:365-76 - PubMed
  11. Contemp Clin Trials. 2012 Nov;33(6):1293-310 - PubMed
  12. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1500-1508.e3 - PubMed
  13. Best Pract Res Clin Gastroenterol. 2019 Jun - Aug;40-41:101634 - PubMed
  14. Neuroimage. 2012 Dec;63(4):1854-63 - PubMed
  15. Gastroenterology. 2016 Feb 13;: - PubMed
  16. Am J Gastroenterol. 2019 Feb;114(2):330-338 - PubMed
  17. PLoS One. 2018 Dec 5;13(12):e0206807 - PubMed
  18. Genome Res. 2009 Sep;19(9):1639-45 - PubMed
  19. Gut. 2011 Sep;60(9):1196-203 - PubMed
  20. Nat Microbiol. 2019 Dec;4(12):2064-2073 - PubMed
  21. Am J Gastroenterol. 2009 Jan;104 Suppl 1:S1-35 - PubMed
  22. J Chromatogr. 1988 Jun 17;442:267-77 - PubMed
  23. Cell. 2015 Apr 9;161(2):264-76 - PubMed
  24. Appl Environ Microbiol. 2005 Dec;71(12):8228-35 - PubMed
  25. Nat Rev Gastroenterol Hepatol. 2017 Jul;14(7):412-420 - PubMed
  26. Curr Protoc Immunol. 2014 Nov 03;107:7.41.1-7.41.11 - PubMed
  27. PLoS One. 2015 Oct 13;10(10):e0140250 - PubMed
  28. Am J Gastroenterol. 2019 Jan;114(1):21-39 - PubMed
  29. Nat Methods. 2010 May;7(5):335-6 - PubMed
  30. Stat Appl Genet Mol Biol. 2004;3:Article3 - PubMed
  31. Cell Mol Gastroenterol Hepatol. 2018 Apr 12;6(2):133-148 - PubMed
  32. Microbiome. 2019 Mar 21;7(1):45 - PubMed
  33. Gastroenterology. 2006 Apr;130(5):1377-90 - PubMed
  34. Microbiome. 2017 May 1;5(1):49 - PubMed
  35. Nat Rev Gastroenterol Hepatol. 2015 Oct;12(10):592-605 - PubMed

Publication Types

Grant support