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Project description:Background and Aims: The pathophysiology of the diarrhoea-predominant inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of colonic biopsies from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and controls to gain insight into CC pathophysiology, identify additional genetic signatures linked to CC, and uncover targets for future therapeutic agents. Methods: We performed whole transcriptome sequencing of CC colonic samples from patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory patients, UC and healthy controls (n=9-13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell gene expression was functionally analyzed by gene-set enrichment and gene-set variation analyses to identify statistically significant pathways and cells, respectively, that change in CC. Leading genes and cells were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared CC transcriptome with that from UC samples. Results: We identified an activation of the adaptive immune response to bacteria in active CC compared to that in remission that could be mediated by dendritic cells. However, a unique signature of genes related to the immune response and DNA transcription remain dysregulated after achieving remission. Budesonide-refractory CC patients fail to restore normal gene expression, which results in a transcriptomic profile close to UC. Intestinal epithelial CC cells displayed an impaired cell proliferation and increased antigen presentation. Conclusion: Our study confirmed previous findings from GWAS and immunological studies related to CC pathogenesis and describes novel genes, pathways and cells that might contribute to the pathophysiology of CC, ongoing epithelial damage, and complications associated with CC.
2021-05-03 | GSE159008 | GEO
Project description:Background and Aims: The pathophysiology of the diarrhoea-predominant inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of colonic biopsies from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and controls to gain insight into CC pathophysiology, identify additional genetic signatures linked to CC, and uncover targets for future therapeutic agents. Methods: We performed whole transcriptome sequencing of CC colonic samples from patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory patients, UC and healthy controls (n=9-13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell gene expression was functionally analyzed by gene-set enrichment and gene-set variation analyses to identify statistically significant pathways and cells, respectively, that change in CC. Leading genes and cells were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared CC transcriptome with that from UC samples. Results: We identified an activation of the adaptive immune response to bacteria in active CC compared to that in remission that could be mediated by dendritic cells. However, a unique signature of genes related to the immune response and DNA transcription remain dysregulated after achieving remission. Budesonide-refractory CC patients fail to restore normal gene expression, which results in a transcriptomic profile close to UC. Intestinal epithelial CC cells displayed an impaired cell proliferation and increased antigen presentation. Conclusion: Our study confirmed previous findings from GWAS and immunological studies related to CC pathogenesis and describes novel genes, pathways and cells that might contribute to the pathophysiology of CC, ongoing epithelial damage, and complications associated with CC.
2021-05-03 | GSE159007 | GEO
Project description:Background and aimsThe pathophysiology of the inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of mucosal samples from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and control subjects to gain insight into CC pathophysiology, identify genetic signatures linked to CC, and uncover potentially druggable disease pathways.MethodsWe performed whole transcriptome sequencing of CC samples from patients before and during treatment with the corticosteroid drug budesonide, CC steroid-refractory patients, UC patients, and healthy control subjects (n = 9-13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell (IEC) gene expression were analyzed by gene set enrichment and gene set variation analyses to identify significant pathways and cells, respectively, altered in CC. Leading genes and cells were validated using reverse-transcription quantitative polymerase chain reaction or immunohistochemistry.ResultsWe identified an activation of the adaptive immune response to bacteria and viruses in active CC that could be mediated by dendritic cells. Moreover, IECs display hyperproliferation and increased antigen presentation in active CC. Further analysis revealed that genes related to the immune response (DUOX2, PLA2G2A, CXCL9), DNA transcription (CTR9), protein processing (JOSD1, URI1), and ion transport (SLC9A3) remained dysregulated even after budesonide-induced remission. Budesonide-refractory CC patients fail to restore normal gene expression, and displayed a transcriptomic profile close to UC.ConclusionsOur study confirmed the implication of innate and adaptive immune responses in CC, governed by IECs and dendritic cells, respectively, and identified ongoing epithelial damage. Refractory CC could share pathomechanisms with UC.
| S-EPMC8267496 | biostudies-literature
Project description:Transcriptomic profiling of collagenous colitis identifies hallmarks of non-destructive inflammatory bowel disease
| PRJNA667340 | ENA
Project description:Transcriptomic profiling of collagenous colitis identifies hallmarks of non-destructive inflammatory bowel disease [Whole mucosa]
| PRJNA667343 | ENA
Project description:Transcriptomic profiling of collagenous colitis identifies hallmarks of non-destructive inflammatory bowel disease [Microdissected IEC]
| PRJNA667344 | ENA
Project description:We report ileum gene expression of 37 controls and 158 patients with either Crohn's disease (n=112), ulcerative colitis (n=44), unclassifed IBD (1), or IBS (1). We contrast gene expression in African American (n=104) versus white (n=25) CD and UC patients.
2020-04-15 | GSE137344 | GEO
Project description:Ileum Transcriptomic Profiling in Inflammatory Bowel Disease
| PRJNA565216 | ENA
Project description: Not available
| S-EPMC8678316 | biostudies-literature
Project description:BackgroundInflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease.MethodsThis prospective study enrolled patients with quiescent Crohn disease and ulcerative colitis, defined as the absence of clinical symptoms (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) and endoscopic remission within the prior year. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy or IBD-related hospitalization or surgery. Biomarkers were tested in a derivation cohort, and their performance was examined in an independent validation cohort.ResultsOur prospective cohort study included 164 patients with IBD (108 with Crohn disease, 56 with ulcerative colitis). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (interleukin-10, glial cell line-derived neurotrophic factor, and T-cell surface glycoprotein CD8 alpha chain) and 4 metabolomic markers (propionyl-L-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models. Proteomic and metabolomic risk scores independently predicted relapse with a combined area under the curve of 0.83. A high proteomic risk score (odds ratio = 9.11; 95% confidence interval, 1.90-43.61) or metabolomic risk score (odds ratio = 5.79; 95% confidence interval, 1.24-27.11) independently predicted a higher risk of relapse over 2 years. Fecal metagenomics showed an increased abundance of Proteobacteria (P = 0.0019, q = 0.019) and Fusobacteria (P = 0.0040, q = 0.020) and at the species level Lachnospiraceae_bacterium_2_1_58FAA (P = 0.000008, q = 0.0009) among the relapses.ConclusionsProteomic, metabolomic, and microbial biomarkers identify a proinflammatory state in quiescent IBD that predisposes to clinical relapse.
| S-EPMC7500522 | biostudies-literature