Project description:Background: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both chronic bowel diseases involving stress. To identify genes differentially expressed in UC and IBS, and to determine whether psychological stress can influence those gene expressions, we conducted this pilot study. Methods: Patients of UC, irritable bowel syndrome (IBS) and normal controls (NC) (n=5 in each group) were recruited. Perceived stress scale (PSS) was adopted to assess psychological stress level. Sigmoid mucosa samples were collected during colonoscopy. Differentially expressed genes (DEGs) of both mRNA and microRNA (DEG-mRNA and DEG-miRNA) were identified by RNA-Seq and microarray, respectively. Weighted gene co-expression network analysis (WGCNA), gene ontology, and microRNA target analysis were performed to identify regulatory relationships and pathways involved. Pearson correlation was performed to identify the relationship between DEGs and PSS score.
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:Irritable bowel syndrome (IBS) is a highly prevalent disorder of the gastrointestinal tract characterized by abdominal pain, bloating, and disturbed bowel function. Here we report on the analysis of microarray expression profiles of sigmoid colon mucosal biopsies from IBS patients and healthy control subjects. Two samples were collected from each individual. From 10 individuals, a third sample was collected 2-3 months after the initial collection. The repeat samples were used to assess the robustness of the expression profiles over different locations within the colon and over time. This analysis revealed a number of differentially expressed genes in IBS patients, which point to functional alterations of specific components of the host defence system and the immune response. This is in support of an important role for peripheral gastrointestinal changes underlying the aetiology of IBS. Two gene probe sets with the most strikingly increased expression in mucosal colon biopsies of IBS patients represent a gene that is, as yet, uncharacterised (DKFZP564O0823). We propose to rename this gene IBS1. We also report on the identification of specific sets of gene probes on the microarray, so-called molecular signatures, which enable the distinction of IBS patients from healthy controls. The expression profiles in IBS are consistent across different sites within the sigmoid colon and are stable over time.
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.
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:The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease pathogenesis has been difficult due to the apparent disconnect between animal and human studies and a lack of an integrated multi-omics view in the context of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.