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Preclinical Mechanisms Collection

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Translational Preclinical Models of IBD

Inflammatory Bowel Diseases® supports the mission of the Crohn's & Colitis Foundation by bringing the most impactful and cutting-edge clinical topics and research findings related to inflammatory bowel diseases (IBD) to clinicians and researchers working in IBD and related fields. The Journal invited technical reviews and original research articles that add to the body of knowledge of the current status of in vivo, ex vivo, in silico, and humanized preclinical models of Crohn’s disease and ulcerative colitis to create the below collection. This collection adds to the understanding of Preclinical Human IBD Mechanisms as described in the Foundation’s Challenges in IBD document.

Basic Science Research

Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation
Zhou Zhou and others
Background Previous work on inflammatory bowel disease (IBD) revealed changes in the abundance of colonic stromal subsets during intestinal inflammation. However, it is currently unknown whether these stromal cell subset changes are also reflected in different IBD mouse models and how commonly used ...
Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury
Jonathan L Golob and others
Background and Aims Inflammation can generate pathogenic T h 17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory T h 17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD ...
A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice
Amruth Chilukuri and others
Background Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene ...
Fecal Myeloperoxidase Levels Reflect Disease Activity in Children With Crohn’s Disease
Teagan S Edwards and others
Background Crohn’s disease (CD) is a major form of inflammatory bowel disease (IBD) which has relapsing and remitting symptoms. Better ways to detect and monitor active disease are required for early diagnosis and optimal outcomes. We assessed fecal myeloperoxidase (fMPO), a neutrophil-derived ...
Macrophage-Derived Exosomes Promoted the Development and Stemness of Inflammatory Bowel Disease-Related Colorectal Cancer via nuclear paraspeckle assembly transcript 1-Mediated miRNA-34a-5p/phosphoprotein enriched in astrocytes 15 Axis
Fen Liu and others
Background Inflammatory bowel disease (IBD) is closely associated with the development of colorectal cancer (CRC) due to the chronic inflammatory response. Macrophages play critical roles in regulating the microenvironment to facilitate tumor progression. Exosomes are key modulators for the ...
The Effect of Colesevelam on the Microbiome in Postoperative Crohn’s Disease
Aditi Kumar and others
Background While surgery plays a pivotal role in the management of ileal Crohn’s disease, the risk of endoscopic recurrence following an ileocaecal resection can be greater than 65% within 12 months of surgery. More than 90% of patients with Crohn’s disease have a concomitant diagnosis of bile acid ...
Targeting NCAPD2 as a Therapeutic Strategy for Crohn’s Disease: Implications for Autophagy and Inflammation
Hao Ge and others
Background Our earlier studies identified that non-SMC condensin I complex subunit D2 (NCAPD2) induces inflammation through the IKK/NF-κB pathway in ulcerative colitis. However, its role in the development of Crohn’s disease (CD) and the specific molecular mechanism still need to be further ...
Eosinophil Depletion as a Potential Therapeutic Strategy in Acute and Chronic Intestinal Inflammation Based on a Dextran Sulfate Sodium Colitis Model
Inge Jacobs and others
Background A role for eosinophils in intestinal inflammation and fibrosis in the context of inflammatory bowel disease has been suggested, yet the precise nature, whether causal or secondary remains debated. Hence, it remains unclear whether targeting eosinophils should be further explored as a ...
Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis
Kensuke Ohishi and others
Background Immune cell populations in the intestinal muscularis propria during colitis are poorly resolved. Maintaining homeostasis in this niche is critical, highlighted by the poorer prognosis of inflammatory bowel disease associated with muscularis propria inflammation. Methods This study ...
Treatment of Active Crohn’s Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products
Caroline Kerbiriou and others
Background Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn’s disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking ...

Basic Science Reviews

Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics
Greg Gibson and others
The past 2 decades have witnessed extraordinary advances in our understanding of the genetic factors influencing inflammatory bowel disease (IBD), providing a foundation for the approaching era of genomic medicine. On behalf of the NIDDK IBD Genetics Consortium, we herein survey 11 grand challenges ...
Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways
Priya Arumugam and others
Intestinal epithelial tight junctions (TJs), a dynamically regulated barrier structure composed of occludin and claudin family of proteins, mediate the interaction between the host and the external environment by allowing selective paracellular permeability between the luminal and serosal ...
The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis
Daniel G Couch and others
Background Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods We systematically reviewed publications on the benefit of drugs targeting ...
Network Medicine: A Mandatory Next Step for Inflammatory Bowel Disease
Heitor S P de Souza and Claudio Fiocchi
Despite unquestionable progress in the management of inflammatory bowel disease (IBD) and the much improved clinical results achievable today in Crohn’s disease (CD) and ulcerative colitis (UC) patients, the overall therapeutic outcome remains far from optimal. The main reason of this partial ...
SAMP1/YitFc mouse strain: A spontaneous model of Crohn's disease-like ileitis
Theresa T. Pizarro and others
The SAMP1/YitFc mouse strain represents a model of Crohn's disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Different from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/YitFc mice ...
Pharmacological intervention studies using mouse models of the inflammatory bowel diseases: translating preclinical data into new drug therapies
Iurii Koboziev and others
Most therapeutic agents used in clinical practice today were originally developed and tested in animal models so that drug toxicity and safety, dose-responses, and efficacy could be determined. Retrospective analyses of preclinical intervention studies using animal models of different diseases ...
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