Genomic and clinical effects associated with a relaxation response mind-body intervention in patients with irritable bowel syndrome and inflammatory bowel disease.
BACKGROUND
Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined.


METHODS
Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI.


RESULTS
Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules.


CONCLUSIONS
In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD-and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding.


BACKGROUND
ClinicalTrials.Gov NCT02136745.
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Braden
B
Kuo
Division of Interdisciplinary Medicine & Biotechnology, and Genomics, Proteomics, Bioinformatics and Systems Biology Center, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America; Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Manoj
M
Bhasin
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Jolene
J
Jacquart
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Matthew A
MA
Scult
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Lauren
L
Slipp
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Eric Isaac Kagan
EI
Riklin
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Veronique
V
Lepoutre
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Nicole
N
Comosa
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Beth-Ann
BA
Norton
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Allison
A
Dassatti
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Jessica
J
Rosenblum
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Andrea H
AH
Thurler
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Brian C
BC
Surjanhata
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Nicole N
NN
Hasheminejad
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Leslee
L
Kagan
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Ellen
E
Slawsby
Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America; Center for Healthcare Organization and Implementation Research (CHOIR), Bedford VA Medical Center, Bedford, Massachusetts, United States of America.
Sowmya R
SR
Rao
MGH Biostatistics Center, Massachusetts General Hospital, Boston, MA, and Harvard Medical School, Boston, Massachusetts, United States of America.
Eric A
EA
Macklin
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Gregory L
GL
Fricchione
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Herbert
H
Benson
Division of Interdisciplinary Medicine & Biotechnology, and Genomics, Proteomics, Bioinformatics and Systems Biology Center, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America; Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Towia A
TA
Libermann
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Joshua
J
Korzenik
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
John W
JW
Denninger
D000293:Adolescent; D000328:Adult; D000368:Aged; D003071:Cognition; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000523:psychology / Q000628:therapy; D043183:Irritable Bowel Syndrome / Q000097:blood / Q000523:psychology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D026441:Mind-Body Therapies; D010865:Pilot Projects; D059467:Transcriptome