Pathogenesis of Intestinal Fibrosis in Inflammatory Bowel Disease and Perspectives for Therapeutic Implication

2017 ◽  
Vol 35 (1-2) ◽  
pp. 25-31 ◽  
Author(s):  
Dominik Bettenworth ◽  
Florian Rieder
Keyword(s):  
Inflammatory Bowel Disease ◽  
Chronic Inflammation ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Stricture Formation ◽  
Intestinal Fibrosis ◽  
Conventional View ◽  
Multiple Cell ◽  
Inflammatory Bowel

Background: Intestinal fibrosis with stricture formation is a common feature of inflammatory bowel disease (IBD) and leads to a significantly impaired quality of life in affected patients, intestinal obstruction as well as to the need for surgical intervention. This constitutes a major treatment challenge. Key Messages: Fibrosis results from the response of gut tissue to the insult inflicted by chronic inflammation. Similarly to what occurs in other organs, the underlying fibrogenic mechanisms are complex and dynamic, involving multiple cell types, interrelated cellular events, and a large number of soluble factors. Owing to a breakdown of the epithelial barrier in IBD, luminal bacterial products leak into the interstitium and induce an innate immune response mediated by the activation of both immune and non-immune cells. Other environmental factors as well as chronic inflammation will certainly impact the quality and quantity of intestinal fibrosis. Finally, the composition of the intestinal extracellular matrix is dramatically altered in chronic gut inflammation and actively promotes fibrosis through its mechanical properties. The conventional view that intestinal fibrosis is an inevitable and irreversible process is gradually changing in light of an improved understanding of the cellular and molecular mechanisms that underline its pathogenesis. In addition, clinical observations in patients who undergo strictureplasty have shown that stricture formation is reversible. Conclusions: Identification of the unique mechanisms of intestinal fibrogenesis should create a practical framework to target and block specific fibrogenic pathways, estimate the risk of fibrotic complications, permit the detection of early fibrotic changes and, eventually, allow the development of treatment methods customized to each patient's type and degree of intestinal fibrosis.

Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Giorgos Bamias ◽  
Theresa T Pizarro ◽  
Fabio Cominelli
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Large Scale ◽  
Intestinal Inflammation ◽  
Temporal Association ◽  
Stricture Formation ◽  
Intestinal Fibrosis ◽  
Matrix Deposition ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Abstract Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.

Role of Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

2018 ◽  
Vol 13 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Sara Lovisa ◽  
Giannicola Genovese ◽  
Silvio Danese
Keyword(s):  
Inflammatory Bowel Disease ◽  
Wound Healing ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Manifestations ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Inflammatory Bowel

Abstract Intestinal fibrosis is an inevitable complication in patients with inflammatory bowel disease [IBD], occurring in its two major clinical manifestations: ulcerative colitis and Crohn’s disease. Fibrosis represents the final outcome of the host reaction to persistent inflammation, which triggers a prolonged wound healing response resulting in the excessive deposition of extracellular matrix, eventually leading to intestinal dysfunction. The process of epithelial-to-mesenchymal transition [EMT] represents an embryonic program relaunched during wound healing, fibrosis and cancer. Here we discuss the initial observations and the most recent findings highlighting the role of EMT in IBD-associated intestinal fibrosis and fistulae formation. In addition, we briefly review knowledge on the cognate process of endothelial-to-mesenchymal transition [EndMT]. Understanding EMT functionality and the molecular mechanisms underlying the activation of this mesenchymal programme will permit designing new therapeutic strategies to halt the fibrogenic response in the intestine.

scholarly journals Angiogenesis in Inflammatory Bowel Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Canan Alkim ◽  
Huseyin Alkim ◽  
Ali Riza Koksal ◽  
Salih Boga ◽  
Ilker Sen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Cell Types ◽  
Research Area ◽  
Complex Process ◽  
Multiple Cell ◽  
Inflammatory Bowel ◽  
New Research ◽  
Chronic Intestinal Inflammation

Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature.

Application of Ultrasound Elastography for Assessing Intestinal Fibrosis in Inflammatory Bowel Disease: Fiction or Reality?

2020 ◽  
Vol 21 ◽  
Author(s):  
Roberto Gabbiadini ◽  
Eirini Zacharopoulou ◽  
Federica Furfaro ◽  
Vincenzo Craviotto ◽  
Alessandra Zilli ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Sample Size ◽  
Bowel Disease ◽  
Small Sample Size ◽  
Shear Wave Elastography ◽  
Small Sample ◽  
Ultrasound Elastography ◽  
Invasive Technique ◽  
Intestinal Fibrosis ◽  
Inflammatory Bowel

Background: Intestinal fibrosis and subsequent strictures represent an important burden in inflammatory bowel disease (IBD). The detection and evaluation of the degree of fibrosis in stricturing Crohn’s disease (CD) is important to address the best therapeutic strategy (medical anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness as a biomarker of intestinal fibrosis. Objective: The aim of this review is to discuss the ability and current role of ultrasound elastography in the assessment of intestinal fibrosis. Results and Conclusion: Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample size. The first type of USE investigated was strain elastography, while shear wave elastography has been introduced lately. Despite the heterogeneity of the methods of the studies, USE has been proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing this technique in current practice, further studies with larger sample size and homogeneous parameters, testing reproducibility, and identification of validated cut-off values are needed.

scholarly journals Thrombotic Complications in Inflammatory Bowel Disease

2019 ◽  
Vol 29 (2) ◽  
pp. 23-26
Author(s):  
A. V. Borota ◽  
A. A. Borota ◽  
E. V. Onishchenko
Keyword(s):  
Inflammatory Bowel Disease ◽  
Chronic Inflammation ◽  
Bowel Disease ◽  
Intestinal Wall ◽  
Coagulation Cascade ◽  
Coagulation System ◽  
Primary Disease ◽  
Prevention And Treatment ◽  
Thrombotic Complications ◽  
Inflammatory Bowel

The risk of thrombotic complications is known to be 3 times higher in patients with inflammatory bowel disease (IBD) than in healthy individuals, with the relative risk being 15 times higher during the periods of relapses. Aim. To study and generalize literature data available on the prevention and treatment of IBD thrombotic complications.Key findings. In the сonditions under study, the presence of chronic inflammation and increased bleeding of the intestinal wall is shown to activate the coagulation system, impair the fibrinolysis system and reduce the activity of natural anticoagulation mechanisms. The concentration of fibrinogen — a protein of the acute inflammation phase — increases significantly. This results in an imbalance of the blood coagulation system with a tendency to hypercoagulation, which significantly increases the risk of thrombotic complications and the disseminated intravascular coagulation syndrome. In turn, the activation of the coagulation cascade may trigger the inflammatory response, which eventually leads to the formation of a vicious circle between chronic inflammation and thrombosis. The pathogenesis of thrombosis in inflammatory colon diseases is a multifactor process, which remains to be understood.Conclusion.The management of patients with IBD in combination with thromboembolic complications requires an individual multidisciplinary approach. Taking into account the pathogenetic factors, the following options are possible in the prevention and treatment of thrombotic complications in IBD: strengthening the basic therapy of the primary disease; administration of prophylactic doses of anticoagulants under dynamic continuous laboratory control in the acute period using the methods of conservative therapy of thrombotic complications (elastic compression of the lower extremities) in the period of exacerbation of the primary disease.

scholarly journals Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhuo Xie ◽  
Mudan Zhang ◽  
Gaoshi Zhou ◽  
Lihui Lin ◽  
Jing Han ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Critical Role ◽  
Signalling Pathway ◽  
Hedgehog Signalling Pathway ◽  
Inflammatory Bowel ◽  
Effective Drugs

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

Effects of dietary tryptophan supplementation in the acetic acid-induced colitis mouse model

2018 ◽  
Vol 9 (8) ◽  
pp. 4143-4152 ◽  
Author(s):  
Shuai Chen ◽  
Meiwei Wang ◽  
Lanmei Yin ◽  
Wenkai Ren ◽  
Peng Bin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Acetic Acid ◽  
Gastrointestinal Tract ◽  
Mouse Model ◽  
Chronic Inflammation ◽  
Bowel Disease ◽  
Intestinal Immunity ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is strongly associated with intestinal immunity and the microbiome.

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