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Systems biology approach highlights mechanistic differences between Crohn's disease and ulcerative colitis.

ABSTRACT: The molecular mechanisms of IBD have been the subject of intensive exploration. We, therefore, assembled the available information into a suite of causal biological network models, which offer comprehensive visualization of the processes underlying IBD. Scientific text was curated by using Biological Expression Language (BEL) and compiled with OpenBEL 3.0.0. Network properties were analysed by Cytoscape. Network perturbation amplitudes were computed to score the network models with transcriptomic data from public data repositories. The IBD network model suite consists of three independent models that represent signalling pathways that contribute to IBD. In the "intestinal permeability" model, programmed cell death factors were downregulated in CD and upregulated in UC. In the "inflammation" model, PPARG, IL6, and IFN-associated pathways were prominent regulatory factors in both diseases. In the "wound healing" model, factors promoting wound healing were upregulated in CD and downregulated in UC. Scoring of publicly available transcriptomic datasets onto these network models demonstrated that the IBD models capture the perturbation in each dataset accurately. The IBD network model suite can provide better mechanistic insights of the transcriptional changes in IBD and constitutes a valuable tool in personalized medicine to further understand individual drug responses in IBD.

SUBMITTER: Ruiz Castro PA

PROVIDER: S-EPMC8169754 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Differences between tissue-associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis.

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| S-EPMC1698347 | biostudies-literature

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-06 | GSE114603 | GEO

Novel biomarkers for neoplastic progression from ulcerative colitis to colorectal cancer: a systems biology approach.

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2018-11-06 | GSE114527 | GEO

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [miRNA-Seq]

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Project description:Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA O- and N-glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care.

| S-EPMC10563165 | biostudies-literature

Plasma microRNA Profile Differentiates Crohn's Colitis From Ulcerative Colitis.

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| S-EPMC5858028 | biostudies-literature

The Human Mesenteric Lymph Node Microbiome Differentiates Between Crohn's Disease and Ulcerative Colitis.

Project description:Background and aimsMesenteric lymph nodes are sites in which translocated bacteria incite and progress immunological responses. For this reason, understanding the microbiome of mesenteric lymph nodes in inflammatory bowel disease is important. The bacterial profile of Crohn's disease mesenteric lymph nodes has been analysed using culture-independent methods in only one previous study. This study aimed to investigate the mesenteric lymph node microbiota from both Crohn's disease and ulcerative colitis patients.MethodsMesenteric lymph nodes were collected from Crohn's disease and ulcerative colitis patients undergoing resection. Total DNA was extracted from mesenteric lymph nodes and assessed for the presence of bacterial DNA [16S]. All work was completed in a sterile environment using aseptic techniques. Samples positive for 16S DNA underwent next-generation sequencing, and the identity of bacterial phyla and species were determined.ResultsCrohn's disease mesenteric lymph nodes had a distinctly different microbial profile to that observed in ulcerative colitis. The relative abundance of Firmicutes was greater in nodes from ulcerative colitis patients, whereas Proteobacteria were more abundant in Crohn's disease. Although species diversity was reduced in the mesenteric lymph nodes of patients with Crohn's disease, these lymph nodes contained greater numbers of less dominant phyla, mainly Fusobacteria.ConclusionThis study confirms that there are distinct differences between the Crohn's disease and ulcerative colitis mesenteric lymph node microbiomes. Such microbial differences could aid in the diagnosis of Crohn's disease or ulcerative colitis, particularly in cases of indeterminate colitis at time of resection, or help explain their mechanisms of development and progression.

| S-EPMC6302955 | biostudies-literature

MicroRNA signatures differentiate Crohn's disease from ulcerative colitis.

Project description:BackgroundExcessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn's disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression.ResultsMicroarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva.ConclusionsOur results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.

| S-EPMC4335694 | biostudies-literature

Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn's disease. An in vivo and in vitro study.

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| S-EPMC3813471 | biostudies-literature

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