Environmental Microbial Factors Determine the Pattern of Inflammatory Lesions in a Murine Model of Crohn’s Disease–Like Inflammation

2019 ◽  
Vol 26 (1) ◽  
pp. 66-79 ◽  
Author(s):  
Iris Stolzer ◽  
Valentina Kaden-Volynets ◽  
Barbara Ruder ◽  
Marilena Letizia ◽  
Miriam Bittel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Murine Model ◽  
Immune Reaction ◽  
Mucosal Barrier ◽  
Bacterial Clearance ◽  
Compelling Evidence ◽  
Susceptible Host ◽  
Inflammatory Lesions ◽  
Mucosal Barrier Function

Here we provide compelling evidence that inflammation in a murine model of Crohn’s disease–like inflammation is characterized by an immune reaction presumably directed at a disease-relevant microflora in a genetically susceptible host with impaired mucosal barrier function and bacterial clearance.

The Role of Immunomodulators and Biologics in the Medical Management of Stricturing Crohn’s Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Iago Rodríguez-Lago ◽  
Javier P Gisbert
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Balloon Dilation ◽  
Endoscopic Balloon Dilation ◽  
Inflammatory Lesions ◽  
Prevention And Treatment ◽  
Inflammatory Changes ◽  
Endoscopic Balloon

Abstract Crohn’s disease is a progressive and disabling inflammatory disease involving the gastrointestinal tract. It usually produces inflammatory lesions in the ileocolonic region, but up to half of patients will also develop complications such as strictures in the long term. Indeed, a proportion of patients have progression of the disease with the development of stricturing lesions because there are no drugs that effectively prevent or reverse established fibrosis, and hence these patients are usually treated with surgery or endoscopic balloon dilation. Fibrotic lesions are always associated with some degree of inflammatory changes, but there is little evidence supporting the use of medical therapy in this context. Here, we discuss the most important findings on the possible use of immunomodulators or biologics in the prevention and treatment of intestinal strictures in Crohn’s disease patients. Recent evidence demonstrates that these drugs may also be effective in treating lesions with high levels of collagen deposition, and thus might, at least in some patients, reduce the progression of the disease and bowel damage, and further avoid the need for surgery and a disabling course in the long term.

T1222 Small Animal PET-CT as a Non-Invasive Method to Evaluate Terminal Ileal Inflammation in a Murine Model of Crohn's Disease

2010 ◽  
Vol 138 (5) ◽  
pp. S-514-S-515 ◽  
Author(s):  
Pieter Hindryckx ◽  
Steven Staelens ◽  
Steven Deleye ◽  
Harald Peeters ◽  
Debby Laukens ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Murine Model ◽  
Small Animal ◽  
Small Animal Pet ◽  
Animal Pet ◽  
Non Invasive ◽  
Pet Ct ◽  
Invasive Method

scholarly journals Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease

2009 ◽  
Vol 206 (10) ◽  
pp. 2301-2301 ◽  
Author(s):  
Andrew M. Smith ◽  
Farooq Z. Rahman ◽  
Bu'Hussain Hayee ◽  
Simon J. Graham ◽  
Daniel J.B. Marks ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Acute Inflammation ◽  
Cytokine Secretion ◽  
Bacterial Clearance ◽  
Macrophage Cytokine

Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn’s disease and infectious colitis

2004 ◽  
Vol 318 (2) ◽  
pp. 313-323 ◽  
Author(s):  
J. A. Hardin ◽  
L. E. Wallace ◽  
J. F. K. Wong ◽  
E. V. O’Loughlin ◽  
S. J. Urbanski ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Murine Model ◽  
Infectious Colitis

1095 Neutrophil Accumulation and Bacterial Clearance Is Delayed in Patients with Crohn's Disease

2009 ◽  
Vol 136 (5) ◽  
pp. A-169
Author(s):  
Bu'Hussain Hayee ◽  
Farooq Rahman ◽  
Andrew M. Smith ◽  
Daniel J. Marks ◽  
Trevor J. Sweeting ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bacterial Clearance ◽  
Neutrophil Accumulation

scholarly journals DOP22 Integrative -omic analysis reveals microbiota mediated molecular mechanisms influencing host mucosal gene expression in Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S061-S062
Author(s):  
P Sudhakar ◽  
T Andrighetti ◽  
S Verstockt ◽  
C Caenepeel ◽  
M Ferrante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Molecular Mechanisms ◽  
Bacterial Species ◽  
Differentially Expressed ◽  
Mucosal Barrier ◽  
Bacterial Proteins ◽  
The Impact ◽  
Hub Proteins

Abstract Background Mechanistic evidence linking gut microbial changes and host mucosal barrier responses in patients with Crohn’s disease (CD) is lacking. In this study, we used a computational approach to integrate gut microbial and intestinal gene expression in CD patients. Methods Bacterial species, bacterial genes/transcripts with enhanced abundances/transcriptional activity in CD (t-statistic of > 2 and Q-value < 0.05), as well as mucosal (ileum/rectum) differentially expressed genes (DEGs) between CD (n =43) and non-IBD (n=22) subjects were retrieved from the Inflammatory Bowel Disease Meta -Omics Database (IBDMDB). The impact of bacterial proteins on host gene expression was inferred using MicrobioLink, a computational tool for inferring microbe-host interactions. Drug target information was retrieved from OpenTargets. Paired 16S read-outs from stool samples and gene expression data from ileal biopsies in CD patients (n=20) and non-IBD controls (n=15), cross-sectionally collected at our IBD referral center, were used for independent validation. Results Across the 8 identified bacterial species enriched in CD, 3.7% (n= 743) of the orthologous groups were identified as being able to bind to human proteins. Network diffusion analysis uncovered bacterial proteins which could cumulatively modulate the expression of 42% of the genes differentially expressed in the ileum of CD patients. Topological and pathway analysis of the inferred signaling network modulated by the microbiota revealed several key hub proteins and immune-related pathways associated with IL-4, IL-2 and IL-13 signaling, receptor tyrosine-kinases, NFkB, and toll-like receptors including TLR4. Seventy-eight percent of the DEGs in our discovery cohort were also differentially expressed in the validation cohort (R2 = 0.907). Bacterial proteins post-translationally modifying host receptors resulted in the up-regulation of several pro-inflammatory cytokines via critical hub proteins such as NFkB (Figure 1). We observed different levels of locational specificity (from 35 to 61%) for the top regulators such as SPI1, STAT1 and NFKB1in terms of genes regulated by them in ileum and rectum. 24 proteins including ITGA4 and JAK1 from the ileal and rectal signaling networks are existing targets of CD drugs such as vedolizumab and tofacitinib, filgotinib and upadacitinib respectively. Conclusion Our findings outline the potential mechanisms of microbiome-induced host responses and provide insights into designing microbiome-mediated therapies to prevent and/or treat CD.

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