Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

Introduction: 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. Trial Registration ClinicalTrials.Gov NCT0213674

Correction: Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease.

[This corrects the article DOI: 10.1371/journal.pone.0123861.]

Pain Catastrophizing Scale scores at each of the four time points in Irritable Bowel Syndrome (IBS, light bars, top) and Inflammatory Bowel Disease (IBD, dark bars, bottom).

<p>*p<0.05, **p<0.01.</p

Transcriptional changes and significantly affected pathways for IBS patients pre- to post-mind body intervention.

<p>A) Heatmap of selected top differentially expressed genes identified by comparing pre- to post-mind body intervention transcriptional profiles. Gene expression is shown with a pseudocolor scale (-1 to 1) with red color denoting increased gene expression post-intervention and green color denoting decreased expression post-intervention. The rows represent the genes and columns represent individual subjects in <b>IBS</b> group. B) Top pathways of genes with altered expression among <b>IBS</b> and IBD patients. Pathway enrichment analysis was performed on differentially expressed genes and significance of effect on pathway was determined using Fisher’s Exact Test p value. Each bar represents a significantly enriched pathway. The p value is depicted as —log10 (p value) on primary X-axis.</p

Outcome measures after intervention and at 3-week follow-up for irritable bowel syndrome (IBS) (N = 19) and inflammatory bowel disease (IBD) (N = 29).

<p>*P<0.05</p><p>**P<0.01</p><p>***P<0.001</p><p>Indicate mixed model analysis estimating change from baseline scores</p><p>Outcome measures after intervention and at 3-week follow-up for irritable bowel syndrome (IBS) (N = 19) and inflammatory bowel disease (IBD) (N = 29).</p

Identification of potential key genes responsible for delivering the beneficial effects of RR-MBI in IBD identified using Gene Set Enrichment Analysis and leading edge analysis.

<p>A) Bar graph depicting the abundance of genes in significantly enriched geneset (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123861#pone.0123861.s003" target="_blank">S2 Fig</a>). B) Heatmap of most abundant genes in <b>IBD</b> patients depicting the pattern of downregulation after the RR-MBI.</p

Disease-specific quality of life and symptom measures at each of the four time points.

<p>A) Irritable Bowel Syndrome Quality of Life (<b>IBS</b>-QOL) scores; lower scores indicate improvement. B) Irritable Bowel Syndrome Symptom Severity Index (<b>IBS</b>-SSI) scores; lower scores indicate improvement. C) Inflammatory Bowel Disease Questionnaire (<b>IBD</b>-Q) scores; higher scores indicate improvement. *p<0.05, **p<0.01, ***p<0.001.</p

The syllabus for the relaxation response-based group mind body intervention (RR-MBI) for irritable bowel syndrome or inflammatory bowel disease.

<p>Session content varied by week but always included an activity that elicited the relaxation response (RR) and a discussion of the homework from the previous week. Homework for the sessions included eliciting the RR daily, daily mini-relaxation exercises, filling out a diary sheet, making an entry in an appreciation journal, and practicing cognitive restructuring exercises and other skills previously learned.</p><p>The syllabus for the relaxation response-based group mind body intervention (RR-MBI) for irritable bowel syndrome or inflammatory bowel disease.</p