scholarly journals Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 81
Author(s):  
Martin Maronek ◽  
Barbora Gromova ◽  
Robert Liptak ◽  
Barbora Konecna ◽  
Michal Pastorek ◽  
...  
Keyword(s):  
Disease Activity ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Relative Proportion ◽  
Extracellular Dna ◽  
Absolute Amount ◽  
Chemically Induced ◽  
Inflammatory Bowel ◽  
Severe Colitis

Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.

scholarly journals Hyaluronan Synthase 3 Null Mice Exhibit Decreased Intestinal Inflammation and Tissue Damage in the DSS-Induced Colitis Model

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sean P. Kessler ◽  
Dana R. Obery ◽  
Carol de la Motte
Keyword(s):  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Experimental Colitis ◽  
Hyaluronan Synthase ◽  
Wild Type ◽  
Colon Tissue ◽  
Dss Colitis ◽  
Chemically Induced ◽  
Inflammatory Bowel ◽  
Colitis Model

Hyaluronan (HA) overproduction is a hallmark of multiple inflammatory diseases, including inflammatory bowel disease (IBD). Hyaluronan can act as a leukocyte recruitment molecule and in the most common mouse model of intestinal inflammation, the chemically induced dextran sodium sulfate (DSS) experimental colitis model, we previously determined that changes in colon distribution of HA occur before inflammation. Therefore, we hypothesized that, during a pathologic challenge, HA promotes inflammation. In this study, we tested the progression of inflammation in mice null for the hyaluronan synthase genes (HAS1, HAS3, or both HAS1 and HAS3) in the DSS-colitis model. Our data demonstrate that both the HAS1/HAS3 double and the HAS3 null mice are protected from colitis, compared to wild-type and HAS1 null mice, as determined by measurement of weight loss, disease activity, serum IL-6 levels, histologic scoring, and immunohistochemistry. Most notable is the dramatic increase in submucosal microvasculature, hyaluronan deposition, and leukocyte infiltration in the inflamed colon tissue of wild-type and HAS1 null mice. Our data suggest, HAS3 plays a crucial role in driving gut inflammation. Developing a temporary targeted therapeutic intervention of HAS3 expression or function in the microcirculation may emerge as a desirable strategy toward tempering colitis in patients undergoing flares of IBD.

scholarly journals The Role of TL1A and DR3 in Autoimmune and Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yoshihiro Aiba ◽  
Minoru Nakamura
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Biliary Cirrhosis ◽  
Tnf Superfamily ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel ◽  
Irritable Bowel

TNF-like ligand 1A (TL1A), which binds its cognate receptor DR3 and the decoy receptor DcR3, is an identified member of the TNF superfamily. TL1A exerts pleiotropic effects on cell proliferation, activation, and differentiation of immune cells, including helper T cells and regulatory T cells. TL1A and its two receptors expression is increased in both serum and inflamed tissues in autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Polymorphisms of theTNFSF15gene that encodes TL1A are associated with the pathogenesis of irritable bowel syndrome, leprosy, and autoimmune diseases, including IBD, AS, and primary biliary cirrhosis (PBC). In mice, blocking of TL1A-DR3 interaction by either antagonistic antibodies or deletion of the DR3 gene attenuates the severity of multiple autoimmune diseases, whereas sustained TL1A expression on T cells or dendritic cells induces IL-13-dependent small intestinal inflammation. This suggests that modulation of TL1A-DR3 interaction may be a potential therapeutic target in several autoimmune diseases, including IBD, RA, AS, and PBC.

scholarly journals P162 Prevalence of nafld (non alcoholic fatty liver disease) and fibrosis in inflammatory bowel disease: the impact of traditional risk factors, intestinal inflammation and genetic phenotype

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S219-S220
Author(s):  
B Scrivo ◽  
C Celsa ◽  
A Busacca ◽  
E Giuffrida ◽  
R M Pipitone ◽  
...  
Keyword(s):  
Risk Factors ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Extraintestinal Manifestations ◽  
Previous Surgery ◽  
Inflammatory Bowel ◽  
Traditional Risk Factors

Abstract Background Prevalence of NAFLD has recently been reported increased in inflammatory bowel disease (IBD) with conflicting results due to heterogeneity of published studies, especially in the diagnostic definition of NAFLD. The increased risk of NAFLD might be related to traditional risk factors but also to IBD-related factors. The role of genetic markers has been addressed only in one study. The aim of our study has been to assess the prevalence of NAFLD and fibrosis in a homogeneous cohort of patients with IBD, assessing the role of metabolic, disease-related and genetic factors. Methods the diagnosis of NAFLD was based on transient fibroelastometry findings (CAP ≥288 dB/m) and HSI (Hepatic Steatosis Index). Demographic data, traditional risk factors for NAFLD (BMI, lipid profile), comorbities, laboratory tests, disease features (type of IBD, duration, extent, extraintestinal manifestations, relapses/year, disease activity, previous surgery, therapy) were registered in a dedicated database. PNPLA3 rs738409 C>G single nucleotide polymorphism, encoding for I148M protein variant, was investigated by Taqman assay. Results 208 consecutive patients were enrolled: 120 males, 121 Crohn’s disease, 87 ulcerative colitis, mean age 46,4 ± 15,2 years. 26 patients (12,5%) were on steroids, 121 on biologics. The prevalence of NAFLD was 20,7% with mean HSI being 38,3 ± 4,7.On univariate analysis, patients with NAFLD were older (54,6 ± 11,1 years), had higher BMI (28,1 ± 3,9 vs. 24,1 ± 3,8), had more frequently hypertension and high level of LDL and tryglicerides. No significant difference was found as far as concerns gender, number of relapses, extraintestinal manifestations, disease activity and duration and ongoing therapy. Medium stiffness value was higher in patients with NAFLD (6,4 ± 2,4 vs. 4,8 ± 2,2 KPa). CG phenotype of PNAPL3 was more frequent among NAFLD patients, though the result was not significant. On multivariate analysis age, BMI, previous surgery and level of stiffness > 6,9 kPa were independently related to NAFLD. Conclusion This single center cross-sectional study shows that, by using transient elastography, the prevalence of NAFLD in IBD is 20,7% with a significantly increase of liver stiffness and development of fibrosis. NAFLD was related to traditional risk factors (age, BMI, lipid profile) and to previous ileal resection, the last probably due to changes of gut microbiota. Neither intestinal inflammation and drugs nor genetic testing for PNAPL3 seem to be related to the development of NAFLD. Longitudinal studies are warranted to assess the progression of fibrosis and the role of therapeutic interventions.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

scholarly journals AB0689 THE IMPORTANCE OF THE SUN. VITAMIN D AND SPONDYLOARTHRITIS: OUR EXPERIENCE IN A THIRD LEVEL HOSPITAL.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1640.2-1640
Author(s):  
I. González Fernández ◽  
C. Álvarez Castro ◽  
C. Moriano ◽  
A. López Robles ◽  
X. E. Larco Rojas ◽  
...  
Keyword(s):  
New York ◽  
Vitamin D ◽  
Disease Activity ◽  
Intestinal Inflammation ◽  
Reference Value ◽  
Hypovitaminosis D ◽  
Lower Severity ◽  
Inflammatory Bowel ◽  
Former Smokers ◽  
Low Levels

Background:Vitamin D plays an important role in the pathogenesis of autoimmune diseases, so that it has been shown that an adequate level is associated with a lower risk of developing this group of entities as well as a lower severity of them. Specifically, in spondyloarthritis (SpA) the deficiency has been associated with greater aggressiveness and greater radiological progression.Objectives:Assess levels of vitamin D in patients diagnosed with SpA in the León University Assistance Complex and study its possible relationship with different clinical-epidemiological variables.Methods:Prospective observational study between January 1, 2019 and December 31, 2019 with consecutive sampling of patients diagnosed with SpA (New York criteria, ASAS) in our hospital between 1973 and 2018. It was taken as a cut-off point for vitamin normality D those values ≥ 30 ng / ml. The disease activity was assessed based on BASDAI and CRP level (taking as a cut-off point 5 mg/l, reference value of our hospital and ruling out elevation due to intercurrent processes) in the last consultation. Positive values above 130 mlg/dL were considered for the orosomucoid and for calprotectin as undetermined values between 50-100 mg/kg feces and suspected IBD greater than 100 mg/kg feces. An attempt was made to link the value of vitamin D with disease activity, tobacco, the development of uveitis and the presence of subclinical intestinal inflammation.Results:132 patients were included, of which 60.6% were men with a mean age of 49.35 ± 12.95 years. 84.8% were B27 positive. 88.6% met New York criteria. 35.6% suffered uveitis at some time during their evolution. As for tobacco, 68.2% were non-smokers, 12.9% were former smokers and 18.9% were active smokers. 6.8% of the sample presented positivity for the orosomucoid and 37.8% alterations in calprotectin (of which 24.2% were undetermined and 13.6% suspected of inflammatory bowel disease). Only 25% of patients had elevated CRP levels and 11.4% of patients had BASDAI> 4. 50.8% of our sample had optimal levels of Vitamin D while 49.2% were at low values.A statistically significant association was observed between hypovitaminosis D and elevated CRP levels (p 0.038). In our sample we found no statistical association with uveitis or with markers of subclinical inflammatory activity.Conclusion:-Almost half of the patients in our sample have hypovitaminosis D which is probably attributable to the meteorological characteristics of León region.-Low levels of vitamin D are statistically significantly related to higher levels of CRP and, therefore, with greater disease activity.-No significant relationship was found with uveitis or with a higher risk of subclinical intestinal inflammation in our simple.References:[1]Castro Domínguez F, Salman Monte TC, Blanch Rubió J. Vitamin D in rheumatic diseases.Rev Osteoporos Metab Miner. 2017; 9 (1) supplement: 31-39.Disclosure of Interests:None declared

Obesity and inflammatory bowel disease

2021 ◽  
Vol 75 (1) ◽  
pp. 20-28
Author(s):  
Vladimír Teplan ◽  
Milan Lukáš
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adipose Tissue ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Perioperative Complications ◽  
Overweight And Obesity ◽  
Special Role ◽  
Low Concentrations ◽  
Inflammatory Bowel

The incidence and prevalence of overweight and obesity has dramatically increased in the last decades and is generally considered to be global pandemics. The incidence of inflammatory bowel disease (IBD) is rising parallel with overweight and obesity. Contrary to a conventional believe, about 15–40% patients with IBD are obese, which can contribute to the development and course of IBD, especially in Crohn’s disease. Although the findings of some cohort studies are still conflicting, recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue known as creeping fat, leading to intestinal inflammation. The involvement of altered adipocyte function and deregulated production of adipokines such as leptin and adiponectin has been suggested in the pathogenesis of IBD. The emerging role of Western diet and microbiota can also open new possibilities in IBD management. The effect of obesity on the IBD-related therapy remains to be studied. The finding that obesity results in suboptimal response to the therapy, potentially promoting rapid clearance of biologic agents and thus leading to their low concentrations, has a great importance. Obesity also makes IBD colorectal surgery technically challenging and might increase a risk of perioperative complications.

scholarly journals Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

2008 ◽  
Vol 105 (46) ◽  
pp. 17931-17936 ◽  
Author(s):  
Danyvid Olivares-Villagómez ◽  
Yanice V. Mendez-Fernandez ◽  
Vrajesh V. Parekh ◽  
Saif Lalani ◽  
Tiffaney L. Vincent ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Genetic Model ◽  
Critical Role ◽  
Intraepithelial Lymphocytes ◽  
Lymphocyte Function ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.

Differential relationships of somatization, depression, and anxiety to severity of Crohn’s disease

2020 ◽  
pp. 135910532090987 ◽  
Author(s):  
Shirley Regev ◽  
Shmuel Odes ◽  
Vered Slonim-Nevo ◽  
Michael Friger ◽  
Doron Schwartz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Structural Equation ◽  
Equation Modeling ◽  
Relative Role ◽  
Depression And Anxiety ◽  
Inflammatory Bowel ◽  
Unique Predictor

Patients with Crohn’s disease, an inflammatory bowel disease, struggle with chronic somatic symptoms that could bring about emotional distress. This study assessed the relative role of somatization, and depressive and anxiety symptoms in disease activity among 619 Crohn’s patients (18–79 years; 58.3% women). Structural equation modeling revealed that somatization was the only unique predictor of disease activity beyond depression and anxiety. In addition, the effect of somatization on disease activity was stronger in men compared to women. Findings suggest that somatization represents a distinct domain of psychological distress that may play a role in the health of patients with Crohn’s disease.

scholarly journals The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease

2019 ◽  
Vol 12 ◽  
pp. 175628481882225 ◽  
Author(s):  
Jonathan P. Segal ◽  
Benjamin H. Mullish ◽  
Mohammed Nabil Quraishi ◽  
Animesh Acharjee ◽  
Horace R. T. Williams ◽  
...  
Keyword(s):  
Systems Biology ◽  
Gut Microbiota ◽  
Potential Role ◽  
Intestinal Inflammation ◽  
Clinical Care ◽  
Complex Interaction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Compositional Changes

The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD. With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD. This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.

scholarly journals Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection

2019 ◽  
Vol 20 (8) ◽  
pp. 1912 ◽  
Author(s):  
Kathryn Burge ◽  
Aarthi Gunasekaran ◽  
Jeffrey Eckert ◽  
Hala Chaaban
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Immunological Response ◽  
Intestinal Microbiome ◽  
Intestinal Barrier Function ◽  
Dietary Antigens ◽  
Inflammatory Bowel ◽  
Intestinal Inflammatory Disease

Intestinal inflammatory diseases, such as Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.

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