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.

Potential of Plant-sourced Phenols for Inflammatory Bowel Disease

2019 ◽  
Vol 25 (38) ◽  
pp. 5191-5217 ◽  
Author(s):  
Hai-tao Xiao ◽  
Bo Wen ◽  
Xiang-chun Shen ◽  
Zhao-xiang Bian
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Term Treatment ◽  
Term Therapy ◽  
Inflammatory Status ◽  
Long Term Treatment ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help further development of new preventive/adjuvant regimens for IBD.

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.

scholarly journals Going Beyond Bacteria: Uncovering the Role of Archaeome and Mycobiome in Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yashar Houshyar ◽  
Luca Massimino ◽  
Luigi Antonio Lamparelli ◽  
Silvio Danese ◽  
Federica Ungaro
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
The Body ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Therefore, the full understanding of the archaeome and mycobiome dysbiosis during IBD pathogenesis may pave the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.

scholarly journals A Rare Form of Chronic Granulomatous Disease (Type Iva) Presenting as Inflammatory Bowel Disease

1996 ◽  
Vol 10 (4) ◽  
pp. 221-224 ◽  
Author(s):  
Francisco A Sylvester
Keyword(s):  
Inflammatory Bowel Disease ◽  
Chronic Granulomatous Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Gastrointestinal Symptoms ◽  
Hypochromic Anemia ◽  
Granulomatous Disease ◽  
Poor Growth ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Neutrophil dysfunction syndromes can sometimes mimic the clinical and pathological features of inflammatory bowel disease. The case of a 3.5-year-old boy with chronic diarrhea, abdominal pain, poor growth since infancy and microcytic, hypochromic anemia is presented. After an extensive diagnostic evaluation, he was found to have a rare variant (type IVA) of chronic granulomatous disease. His gastrointestinal symptoms markedly improved during therapy with gamma-interferon. Chronic granulomatous disease can present initially with a clinical picture suggestive of chronic intestinal inflammation. Therefore it should be considered in the differential diagnosis of atypical inflammatory bowel disease, both in children and young adults.

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibits the IL-6/STAT3 signaling pathway

2021 ◽  
Author(s):  
Zhengquan Yu ◽  
Min Deng ◽  
Xi Wu ◽  
Xiaoyue Duan ◽  
Jiuzhi Xu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Lactobacillus Paracasei ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidences indicate that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant...

scholarly journals Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation

2017 ◽  
Vol 23 (6) ◽  
pp. 497-505 ◽  
Author(s):  
Minesh Mehta ◽  
Shifat Ahmed ◽  
Gerald Dryden
Keyword(s):  
Inflammatory Bowel Disease ◽  
Innate Immunity ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

scholarly journals Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice.

1996 ◽  
Vol 184 (2) ◽  
pp. 707-715 ◽  
Author(s):  
A Mizoguchi ◽  
E Mizoguchi ◽  
C Chiba ◽  
A K Bhan
Keyword(s):  
Inflammatory Bowel Disease ◽  
B Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Embryonic Stem ◽  
Disease Process ◽  
Mutant Mice ◽  
Lymphoid Follicles ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

T cell receptor-alpha mutant mice (TCR-alpha-/-), created by gene targeting of the TCR-alpha gene in embryonic stem cells, spontaneously develop inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymphoid tissue is likely to play an important role in the development of chronic intestinal inflammation, we examined the changes in the appendix lymphoid follicle (ALF) and Peyer's patches (PP) in these mice. We found the structure of the ALF to be remarkably similar to that of the PP in the small intestine; in both instances, lymphoid follicles covered by surface epithelium (dome-formation) were found. The amount of proliferation in the lymphoid follicles of the appendix estimated by in vivo incorporation of 5-bromo-2'deoxyuridine was more than two times that of PP in TCR-alpha-/- mice. ELISPOT assay showed an increase of IgA, IgG1, and IgG2a, but not IgM-secreting B cells in ALF of TCR-alpha-/- mice compared to TCR-alpha+/- control mice. Furthermore, TCR-alpha-/- mice revealed an increase of autoantibody-producing B cells against the cytoskeletal protein tropomyosin in ALF as compared to PP. When TCR-alpha-/- mice underwent appendectomy at a young age (3-5 wk), the number of mesenteric lymph nodes cells at 6-7 mo were markedly less than in the sham-operated TCR-alpha-/- mice. Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In contrast, approximately 80% of controls, including the sham-operated TCR-alpha-/- mice, developed IBD during this period. These results suggest that ALF, rather than PP, is the priming site of cells involved in the disease process and plays an important role in the development of IBD in TCR-alpha-/- mice.

scholarly journals Colorectal Cancer in Inflammatory Bowel Disease

2018 ◽  
Vol 31 (03) ◽  
pp. 168-178 ◽  
Author(s):  
Peter Higgins ◽  
Ryan Stidham
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Detection Techniques ◽  
Clinical Scenarios ◽  
Increased Risk ◽  
Consensus Statements ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

AbstractPatients with inflammatory bowel disease (IBD) are at significantly increased risk of colorectal cancer (CRC), principally resulting from the pro-neoplastic effects of chronic intestinal inflammation. Epidemiologic studies continue to highlight the increased risk of CRC in IBD. However, the incidence has declined over the past 30 years, attributed to both successful CRC-surveillance programs and improved control of mucosal inflammation. Risk factors that further increase the risk of IBD-related CRC include disease duration, extent and severity, the presence of inflammatory pseudopolyps, coexistent primary sclerosing cholangitis, and a family history of CRC. All major professional societies agree that IBD-CRC surveillance should occur more frequently than in the general population. Yet, guidelines and consensus statements differ on the surveillance schedule and preferred method of surveillance. Improved sensitivity to previously “invisible” flat dysplastic lesions using high definition and chromoendoscopy methods has resulted in many guidelines abandoning requirements for random untargeted biopsies of the colon. While colonic dysplasia remains a worrisome finding, and several clinical scenarios remain best addressed by total proctocolectomy due to concerns of synchronous undetected lesions and the unpredictable tempo of progression to malignancy, better detection techniques have also increased opportunities for endoscopic resection of dysplastic lesions that can be clearly delineated. Finally, the expanding armamentarium of medical options in IBD, including anti-tumor necrosis factor and anti-adhesion biologic therapies, have substantially improved our ability to control severe inflammation and likely reduce the risk of CRC over time.

Risk of Neurodegenerative Diseases in Patients with Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study

2021 ◽  
Author(s):  
Ga Hee Kim ◽  
Yeong Chan Lee ◽  
Tae Jun Kim ◽  
Eun Ran Kim ◽  
Sung Noh Hong ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Neurodegenerative Diseases ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Disease Risk ◽  
Population Based ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Nested Case Control ◽  
Chronic Intestinal Inflammation

Abstract Background and Aims Although recent studies have reported that inflammatory bowel disease [IBD] is associated with the development of neurodegenerative diseases via chronic intestinal inflammation and the gut-brain axis, there is insufficient evidence supporting this notion. The aim of this study was to determine the risk of neurodegenerative diseases including Parkinson’s disease [PD] and Alzheimer’s disease [AD] in patients with IBD. Methods Using the National Health Insurance Service data for the entire Korean population, we identified patients with IBD and controls from 2009 to 2011 and followed them up until 2017. We selected the controls in a 1:4 ratio based on age and sex for comparison with cases. Results Of 24 830 IBD patients and 99 320 non-IBD controls, 98 IBD patients and 256 controls developed PD, and 644 IBD patients and 2303 controls developed AD. The overall neurodegenerative disease risk was higher in IBD patients (PD: adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.24-1.97; AD: adjusted HR, 1.14; 95% CI, 1.05-1.25). Younger IBD patients aged 40-65 years had a higher risk of PD compared with controls [adjusted HR, 2.34; 1.63-3.35]. In contrast, patients aged ≥65 years had an increased risk of AD compared with controls [adjusted HR, 1.14; 1.04-1.25]. In a nested case-control study of the IBD cohort, patients aged ≥65 years and the female sex were risk factors for AD, whereas living in an urban area was protective against AD. Conclusions The risk of neurodegenerative diseases was higher in IBD patients than in the non-IBD population.

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