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Differences in tissue populations following hematopoietic stem cell transplantation in Crohn’s disease patients

ABSTRACT: Treatment of severely refractory Crohn’s disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients (n=18) receiving autologous HSCT and non-IBD patients (n=19) to elucidate the mechanism of interaction with the microorganisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139179 | GEO | 2020/10/22

REPOSITORIES: GEO

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Differences in tissue immune cell populations following hematopoietic stem cell transplantation in Crohn’s disease patients

Project description:Treatment of severely refractory Crohn’s disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT.

2019-01-23 | GSE115390 | GEO

Differences in microbiome populations following hematopoietic stem cell transplantation in Crohn?s disease patients

Project description:Treatment of severely refractory Crohn’s disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients (n=18) receiving autologous HSCT. We studied changes in the microbiome induced by HSCT and some non-CD samples.

2020-10-22 | GSE139680 | GEO

Expression data from whole blood in CD patients undergoing HSCT.

Project description:Treatment of severely refractory Crohn’s disease (CD) patients remains a clinical challenge. Recent studies show efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however the mechanisms are incompletely understood. We followed a group of patients (n=18) receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy we compared the immunological changes induced by HSCT in responders and non-responders.

2019-01-23 | GSE100922 | GEO

RNA-seq of nonstenotic and stenotic areas of patients with Crohn’s disease

Project description:Fibrostenotic disease is a common complication in Crohn’s disease (CD). We performed bulk RNA sequencing (n=16) of paired intestinal biopsies taken from nonstenotic and stenotic areas of patients with CD (n=8).

2023-04-26 | E-MTAB-12788 | biostudies-arrayexpress

Expression Profiles of Circular RNAs in colon biopsies from Crohn’s Disease Patients by Microarray Analysis

Project description:To investigate the expression profiles of circRNAs in colon tissues of the patients with Crohn’s Disease(CD) , ulcerative colitis (UC) and healthy controls (HC), we used circRNA microArray analysis form Arraystar to examine the expression of circRNAs in colon tissues of CD,UC and HC.

2019-05-30 | GSE131911 | GEO

Altered Intestinal Microbiota-Host Mitochondria Crosstalk in New Onset Crohn’s Disease

Project description:Intestinal microbial dysbiosis is associated with Crohn’s disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. To evaluate causality and mechanisms of disease, we conducted a systems level study of the interactions between the gut microbiota and host in new-onset pediatric patients. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. A downregulation of mitochondrial proteins implicated in H2S detoxification was observed, while the relative abundance of H2S microbial producers was increased. Network correlation analysis identified Atopobium parvulum as the central hub of H2S producers. Gnotobiotic and conventionalized colitis-susceptible interleukin-10-deficient (Il10-/-) mice demonstrated that A. parvulum induced colitis, a phenotype requiring the presence of the intestinal microbiota. Administration of bismuth, a H2S scavenger, prevented A. parvulum-induced colitis in Il10-/- mice. This study identified host-microbiota interactions that are disturbed in CD patients providing mechanistic insights on CD pathogenesis.

2016-09-29 | PXD002882 | Pride

Dynamics of genome alterations in Crohn’s disease associated colorectal carcinogenesis

Project description:To determine the pattern of copy number alterations that characterizes Crohn’s disease associated colorectal carcinomas (CD-CRCs), we performed array-based comparative genomic hybridization (aCGH) of CD-CRCs. As control group, we used histomorphologically similar sporadic mucinous colorectal adenocarcinomas. To gain insight into the dynamics of copy number alterations in CD associated colorectal tumor development, we additionally analyzed non-dysplastic, i.e., normal or inflamed, mucosa samples and dysplastic lesions from CD-CRC patients by aCGH. This revealed the gain of chromosome arm 5p as a distinctive feature of CD related colorectal carcinogenesis, while the overall pattern of copy number changes in CD-CRC was similar to sporadic mucinous CRC, including gains of chromosomes and chromosome arms 7, 8, 13 and 20q, and losses of 5q, 8p, 17p and 18q.

2018-06-30 | GSE113015 | GEO

Gut multi-omics profiling in Crohn’s disease: A preliminary study

Project description:Background: Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to intestinal microbiota. To assess gut bacterial community, microRNA (miRNA), and short chain fatty acid (SCFA) signatures associated with the activity of Crohn’s disease (CD). Methods: DNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16s rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively. Results: Pairwise comparisons showed that 11 and 27 taxa differed between controls and CD patients with active and inactive disease, respectively. Seven taxa were common to both comparisons, whereas eight taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value <0.05; FC >1.5) in CD patients and controls. Comparisons of controls with CD patients having active and inactive disease identified 12 and seven significantly different miRNAs, respectively. Of six SCFAs, the levels of two differed significantly (p-value <0.05, FC >1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with high discriminatory powers (AUC >0.9) for bacteria and miRNA. The levels of 14 miRNAs and 39 bacterial taxa correlated with the level of SCFAs. Conclusion: CD-related gut dysbiosis correlates significantly with miRNA and SCFA profiling, indicating complex relationships among all these factors in response to intestinal inflammation.

2020-08-10 | GSE144535 | GEO

Ileal S100A9 expression distinguishes Crohn’s disease patients by age at diagnosis

Project description:Crohn’s disease (CD) is a debilitating gastrointestinal disorder that can impact the entirety of the GI tract. While substantial progress has been made in the medical management of CD, it remains incurable, frequently relapses, and is a significant financial and medical burden. The pathophysiology of CD is not well understood, but it is thought to arise in genetically susceptible individuals upon an environmental insult. Further elucidation of the disease etiology promises to expose additional therapeutic avenues, with the hope of reducing the burden of CD. One approach to understanding disease pathophysiology is to identify clinically relevant molecular disease subsets using transcriptomics. In this report, we use hierarchical clustering of the ileal transcriptomes of 34 patients to identify two CD subsets. Clinically, these clusters differed in the age of the patients at CD diagnosis, suggesting that age of disease onset impacts the pathophysiology of the disease. We found that the ileal transcriptomes of the early diagnosis cluster are enriched in inflammatory transcripts, including S100A9, which encodes a calprotectin subunit. Furthermore, levels of S100A9 distinguished individuals diagnosed before the age of 30 from those diagnosed after 30. Together, these findings suggest that medical management of CD patients should consider their age at diagnosis and therapeutic blockade of calprotectin may be beneficial in patients diagnosed earlier in life.

2022-06-02 | GSE151686 | GEO

The Gut Microbiota Metabolite Succinate promotes Adipose Tissue Browning in Crohn’s Disease

Project description:In Crohn’s disease (CD), microbe-host interactions are altered, with changes in microbial’s communities and barrier defects leading to translocation of microbes to surrounding adipose tissue (AT). We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes.

2022-09-14 | PXD030520 | Pride

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