Project description:IBS: Patients who have undergone a diagnostic program for gastrointestinal symptoms and where the diagnosis irritable bowel syndrome was reached. UC: Patients with well-diagnosed ulcerative colitis
Project description:A role for immunoproteasome in the regulation of intestinal permeability has been previously suggested both in mice during water avoidance stress (WAS) and in patients with irritable bowel syndrome (IBS). We thus aimed (i) to evaluate the colonic proteome in wild-type (wt) and β2i immunoproteasome subunit knock-out (β2i-/-) mice during WAS and (ii) to investigate the colonic expression of 49 ubiquitinated-proteins in diarrhea-predominant IBS patients (IBS-D).
Project description:The Cytolethal Distending Toxin (CDT) is a bacterial genotoxin that promotes persistent bacterial colonization during infection and is associated with many inflamatory disorders and cancer. At the cellular level, CDT induces DNA damage and inflammatory signatures in host cells. The aim of this study was to better understand the links betwen CDT-mediated genotoxic activity and immunomodulatory effects. HeLa cells were exposed to a chronic (8 weeks) treatment to 0.25 ng/ml of wild-type (WT) or the catalytic mutant H153A (HA) of CDT from Escherichia coli and transcription analysis was performed using Agilent Sureprint G3 Human GE v2 8x60k microarray.
Project description:Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammationinduced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteriaepithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer’s patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.
Project description:Patients with chronic illnesses such as Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD) often have reduced quality of life. IBS is characterized by abdominal pain/discomfort associated with altered bowel function, such as diarrhea or constipation, without gross structural changes or inflammation [1]; IBD is characterized by gross inflammation in the gastrointestinal (GI) tract which can result in symptoms such as abdominal pain, cramping, diarrhea and bloody stools. IBS and 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. In this study IBS and 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. We performed Peripheral blood transcriptome analysis to identify genomic correlates of the RR-MBI.
