scholarly journals Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
D Dimer

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

scholarly journals Frailty in inflammatory bowel diseases: an emerging concept

2021 ◽  
Vol 14 ◽  
pp. 175628482110254
Author(s):  
Bharati Kochar ◽  
Ariela R. Orkaby ◽  
Ashwin N. Ananthakrishnan ◽  
Christine S. Ritchie
Keyword(s):  
Older Adults ◽  
Inflammatory Bowel Diseases ◽  
Conceptual Models ◽  
Younger Adults ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Relationship ◽  
Improve Health

Inflammatory bowel diseases (IBD), consisting of Crohn’s disease and ulcerative colitis, are chronic remitting, relapsing inflammatory conditions of the gastrointestinal tract. While traditionally a disease of younger ages, the number of older adults with IBD is rising rapidly. Patients with IBD often experience geriatric syndromes at earlier ages. Older adults with IBD have poorer disease and treatment-related outcomes compared with younger adults with IBD. Applying the principles of geriatrics to understanding a chronic disease in older adults may improve health span. Better tools are needed to stratify IBD patients who are at high risk for adverse events. Frailty is a geriatric construct that may approximate biologic age. Frailty is a complex, multi-dimensional syndrome that leads to increased vulnerability to stress and decline of reserve across multiple physiologic systems. In this review, we present the leading conceptual models of frailty and discuss the applications of frailty in immune-mediated diseases. We also review chronic conditions where frailty has been applied successfully as a tool for risk stratification. Finally, we discuss in the detail the growing body of literature highlighting the relationship between frailty and IBD, the epidemiology of frailty in IBD, and ramifications of frailty in IBD.

Su1280 Impaired Intestinal Barrier Function Contributes to the Activation of Coagulatory Cascade in Inflammatory Bowel Diseases

2015 ◽  
Vol 148 (4) ◽  
pp. S-460
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura F. Pisani ◽  
Elena Vianello ◽  
Nadia Munizio ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Barrier Function ◽  
Structural Integrity ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.

scholarly journals Anthocyanins and intestinal barrier function: a review

2019 ◽  
Vol 5 ◽  
pp. 18-30 ◽  
Author(s):  
Jonathan C. Valdez ◽  
Bradley W. Bolling
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Berry Anthocyanins ◽  
Chronic Intestinal Inflammation

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells

2020 ◽  
Vol 11 (4) ◽  
pp. 3741-3748 ◽  
Author(s):  
Wei Li ◽  
Mingbo Gao ◽  
Ting Han
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Vital Role ◽  
Inflammatory Factors ◽  
Barrier Dysfunction ◽  
Lycium Barbarum ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Lycium Barbarum Polysaccharides

Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases.

scholarly journals Evidence for a Potential Role of Metallothioneins in Inflammatory Bowel Diseases

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Anouk Waeytens ◽  
Martine De Vos ◽  
Debby Laukens
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Potential Role ◽  
Current Knowledge ◽  
Zinc Homeostasis ◽  
Central Position ◽  
Small Proteins ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are a group of chronic, relapsing, immune-mediated disorders of the intestine, including Crohn's disease and ulcerative colitis. Recent studies underscore the importance of the damaged epithelial barrier and the dysregulated innate immune system in their pathogenesis. Metallothioneins (MTs) are a family of small proteins with a high and conserved cysteine content that are rapidly upregulated in response to an inflammatory stimulus. Herein, we review the current knowledge regarding the expression and potential role of MTs in IBD. MTs exert a central position in zinc homeostasis, modulate the activation of the transcription factor nuclear factor (NF)-B, and serve as antioxidants. In addition, MTs could be involved in IBD through their antiapoptotic effects or through specific immunomodulating extracellular effects. Reports on MT expression in IBD are contradictory but clearly demonstrate a deviant MT expression supporting the idea that these aberrations in IBD require further clarification.

Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells

2013 ◽  
Vol 304 (11) ◽  
pp. G970-G979 ◽  
Author(s):  
Andreas Fischer ◽  
Markus Gluth ◽  
Ulrich-Frank Pape ◽  
Bertram Wiedenmann ◽  
Franz Theuring ◽  
...  
Keyword(s):  
Tight Junction ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Model Systems ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Junction Proteins

Intestinal barrier dysfunction is pivotal in the etiology of inflammatory bowel diseases. Combined clinical and endoscopic remission (“mucosal healing”) in patients who received anti-TNF-α therapies suggests restitution of the intestinal barrier, but the mechanisms involved are largely unknown. We therefore investigated the impact of the anti-TNF-α antibody adalimumab on barrier function in two in vitro models. Combined stimulation of Caco-2 and T-84 cells with interferon-γ and TNF-α resulted in a significant decrease of transepithelial electrical resistance (TEER) within 6 h that was prevented by adalimumab in concentrations down to 100 ng/ml. Adalimumab furthermore antagonized the appearance of irregular membrane undulations and prevented internalization of tight junction proteins upon cytokine exposure. In addition, TNF-α induced a downregulation of claudin-1, claudin-2, claudin-4, and occludin as well as activation of phosphatidylinositol 3-kinase signaling in T-84 but not Caco-2 cells, which was reversed by adalimumab. At the signaling level, adalimumab prevented increased phosphorylation of myosin light chain as well as activation of p38 MAPK and NF-κB accompanying the decline in TEER in both model systems. Pharmacological inhibition of NF-κB signaling partially prevented the TNF-α-induced TEER loss, whereas inhibition of p38 worsened barrier dysfunction in Caco-2 but not T-84 cells. Taken together, these data demonstrate that adalimumab prevents barrier dysfunction induced by TNF-α both functionally and structurally as well as at the level of signal transduction. Barrier protection might therefore constitute a novel mechanism how anti-TNF-α therapy contributes to epithelial restitution and tissue repair in inflammatory bowel diseases.

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