Project description:Intervention1: NIL: NIL
Control Intervention1: NIL: NIL
Primary outcome(s): 1). Comparative difference in gut microbial signatures in healthy individuals, colorectal (CRC) and ulcerative colitis (UC) patients using BugSpeaks microbiome analytical platform
2). Comparative difference in stool metabolites in healthy individuals, CRC and UC patients
Timepoint: Screening Visit (Up to day 3) Baseline Visit- Day 0
Project description:Objective: Ulcerative colitis (UC) is a chronic disease with rising incidence and unclear etiology. The application of mass spectrometry-based post-genomic analysis methods shall support the development of molecular biomarker signatures providing status information with regard to UC pathomechanisms. Design: Pathomechanisms characteristic for UC were assessed by proteome profiling of human tissue specimen, obtained from five distinct colon locations each of 12 patients. Systemic disease-associated alterations were investigated by mass spectrometry-based multi-omics analyses comprising proteins, metabolites and eicosanoids of plasma obtained from UC patients during disease and upon remission in comparison to healthy controls. Results: Proteome profiling results identified colitis-associated activation of neutrophils, macrophages, B- and T-cells, platelets, fibroblasts and endothelial cells and indicated hypoxic stress, as well as a general reduction of mitochondrial proteins accompanying the establishment of apparent healing-promoting activities as well as scar formation. While the immune cells mainly contributed pro-inflammatory proteins, the colitis-associated epithelial cells, fibroblasts, endothelial cells and platelets predominantly formed anti-inflammatory and healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulation of bile acids, eicosanoids and gut microbiome-derived metabolites. Upon remission, several, but not all, molecular candidate biomarker levels recovered to normal levels. These findings may indicate that pathomechanisms related to gut functions, gut microbiome status, microvascular damage and metabolic dysregulation associated with hypoxia may do not resolve uniformly upon remission. Conclusions: The establishment of disease-associated biomarker profiles related to molecular UC pathomechanisms may support the establishment of bioassays with improved prognostic power aiding individualized therapy.
Project description:Genome wide miRNA profiling of ulcerative colitis, and normal colon mucosa samples. The GeneChip miRNA 3.0 Array was used to obtain miRNA profiles across colon mucosa samples. Samples came from 5 ulcerative colitis affected, and 5 normal individuals.
Project description:Genome wide expression profiling of ulcerative colitis, and normal colon mucosa samples. The GeneChip PrimeView Human Gene Expression Array was used to obtain expresion profiles across colon mucosa samples. Samples came from 5 ulcerative colitis affected, and 5 normal individuals.
Project description:The etiology of the inflammatory bowel diseases, including ulcerative colitis, remains incomplete, but recent findings points to the involvement of complex host-microbial interactions. We hypothesized that an analysis of the proteins on the host-microbial interacting surface, the intestinal mucosa, could reveal novel insights into the diseases. Mucosal colonic biopsies were extracted by standard colonscopy from sigmoideum from 10 ulcerative colitis patients from non-inflammed tissue and 10 controls. The biopsies were immediately following extraction snap-frozen for protein analysis and the protein content of the biopsies was characterized by high-throughput quantative gel-free proteomics.
Project description:Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission. We performed a whole-genome transcriptional analysis of colonic biopsies from patients with histologically active and inactive UC, as well as non-inflammatory controls.
Project description:Genome wide DNA methylation profiling of Crohn's disease, ulcerative colitis, and normal colon mucosa samples. The Illumina Infinium HumanMethylation450 BeadChip v1.1 was used to obtain DNA methylation profiles across 482,421 CpGs in colon mucosa samples. Samples came from 10 Crohn's disease affected, 4 ulcerative colitis affected, and 10 normal individuals. One ulcerative colitis sample was assayed before and after treatment with 6-mercaptopurine and mesalamine.
Project description:Genome wide DNA methylation profiling of Crohn's disease, ulcerative colitis, and normal colon mucosa samples. The Illumina Infinium HumanMethylation450 BeadChip v1.1 was used to obtain DNA methylation profiles across 482,421 CpGs in colon mucosa samples. Samples came from 5 Crohn's disease affected, 5 ulcerative colitis affected, and 12 normal individuals. One ulcerative colitis sample was assayed before and after treatment with infliximab and mesalamine.
Project description:Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission. We performed a whole-genome transcriptional analysis of colonic biopsies from patients with histologically active and inactive UC, as well as non-inflammatory controls. Ulcerative colitis patients and non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for UC patients were: age between 18 and 65, diagnosis of UC established at least 6 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and histologic score: Mayo sub score >=2 and MATTS >=3 respectively . Inactive disease was also defined by endoscopic and histologic score: Mayo sub score =0 and MATTS <=2 respectively, and a remission state for a minimum of 5 month prior to biopsy collection, and remained inactive for at least 6 months after. Uninvolved mucosa from patients with active UC was defined as a colonic segment with completely normal endoscopic appearance, normal histology, and absence of any previous evidence of active disease. Finally, a total of 43 biopsies were analyzed: 13 healthy controls, 8 inactive UC, 7 non-involved active UC and 15 involved active UC.
Project description:This study contains multiple -omic data sets. As a follow up to a study on 40 Ulcerative Colitis patients (MSV000082094), 210 fecal samples were analyzed through proteomics using Tandem Mass Tag (TMT) MS3 quantitation. Samples include both Ulcerative Colitis and Crohn's disease patients with healthy volunteers for context. Fecal samples were also analyzed by metabolomics through LCMS2 on a Bruker Maxis qTOF.