scholarly journals Understanding Host-Adherent-InvasiveEscherichia coliInteraction in Crohn’s Disease: Opening Up New Therapeutic Strategies

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Allison Agus ◽  
Sébastien Massier ◽  
Arlette Darfeuille-Michaud ◽  
Elisabeth Billard ◽  
Nicolas Barnich
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Opportunistic Pathogens ◽  
Epithelial Barrier Function ◽  
New Treatment ◽  
Opening Up ◽  
Mammalian Intestine ◽  
Stimulation Of

A trillion of microorganisms colonize the mammalian intestine. Most of them have coevolved with the host in a symbiotic relationship and some of them have developed strategies to promote their replication in the presence of competing microbiota. Recent evidence suggests that perturbation of the microbial community favors the emergence of opportunistic pathogens, in particular adherent-invasiveEscherichia coli(AIEC) that can increase incidence and severity of gut inflammation in the context of Crohn’s disease (CD). This review will report the importance of AIEC as triggers of intestinal inflammation, focusing on their impact on epithelial barrier function and stimulation of mucosal inflammation. Beyond manipulation of immune response, restoration of gut microbiota as a new treatment option for CD patients will be discussed.

scholarly journals Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Grégoire Chevalier ◽  
Arnaud Laveissière ◽  
Guillaume Desachy ◽  
Nicolas Barnich ◽  
Adeline Sivignon ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Bacterial Adhesion ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Intestinal Epithelial ◽  
E Coli ◽  
Promising Therapeutic Approach ◽  
Activity Dependent

Abstract Background An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn’s Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD. Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS. Therefore, targeting the bacterial adhesion of FimH-expressing bacteria seems a promising therapeutic approach, consisting of disarming bacteria without killing them, representing a selective strategy to suppress a potentially critical trigger of intestinal inflammation, without disturbing the intestinal microbiota. Results We analyzed the metagenomic composition of the gut microbiome of 358 patients with CD from two different cohorts and characterized the presence of FimH-expressing bacteria. To assess the pathogenic role of FimH, we used human intestinal explants and tested a specific FimH blocker to prevent bacterial adhesion and associated inflammation. We observed a significant and disease activity-dependent enrichment of Enterobacteriaceae in the gut microbiome of patients with CD. Bacterial FimH expression was functionally confirmed in ileal biopsies from 65% of the patients with CD. Using human intestinal explants, we further show that FimH is essential for adhesion and to trigger inflammation. Finally, a specific FimH-blocker, TAK-018, inhibits bacterial adhesion to the intestinal epithelium and prevents inflammation, thus preserving mucosal integrity. Conclusions We propose that TAK-018, which is safe and well tolerated in humans, is a promising candidate for the treatment of CD and in particular in preventing its recurrence.

scholarly journals Imbalance of the interleukin 1 system in colonic mucosa—association with intestinal inflammation and interleukin 1 receptor agonist genotype 2

Gut ◽  
1997 ◽  
Vol 41 (5) ◽  
pp. 651-657 ◽  
Author(s):  
T Andus ◽  
R Daig ◽  
D Vogl ◽  
E Aschenbrenner ◽  
G Lock ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Colonic Mucosa ◽  
Intestinal Inflammation ◽  
Interleukin 1 ◽  
Mucosal Inflammation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Biopsy Specimens ◽  
Genotype 2 ◽  
Normal Controls

Background—Interleukin 1 (IL-1) α and β are potent cytokines which play key roles in inflammation. They are controlled by IL-1 receptor antagonist (IL-1ra).Aims—To investigate the influence of mucosal inflammation and IL-1ra genotype on the IL-1ra:IL-1 balance.Patients and methods—IL-1α, IL-1β, and IL-1ra were measured by enzyme linked immunosorbent assay (ELISA) in biopsy specimens taken from inflamed and non-inflamed colon of 60 patients with Crohn’s disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls. IL-1ra genotype was determined by polymerase chain reaction and gel electrophoresis.Results—IL-1α and IL-1β were significantly increased in inflamed mucosa in inflammatory bowel disease (IBD) (CD: 53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectively; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2 (7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared with normal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respectively). In CD IL-1α and β were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectively; p<0.0012). IL-1ra:(IL-1α+β) ratios were significantly decreased in inflamed mucosa of patients with CD (182 (45); p<0.0001), UC (425 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and in non-inflamed mucosa in CD (369 (149); p<0.0001) compared with normal controls (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 had slightly but significantly reduced mucosal IL-1ra concentrations (p=0.003). The greatest difference was seen in colonic biopsy specimens from patients with inflamed Crohn’s disease.Conclusion—Mucosal inflammation can modulate the balance of the IL-1:IL-1ra system in colonic mucosa.

Mincle/Syk Signalling Promotes Intestinal Mucosal Inflammation Through Induction of Macrophage Pyroptosis in Crohn’s Disease

2020 ◽  
Vol 14 (12) ◽  
pp. 1734-1747
Author(s):  
Wenbin Gong ◽  
Tao Zheng ◽  
Kun Guo ◽  
Miao Fang ◽  
Haohao Xie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Proinflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
Experimental Colitis ◽  
Mitogen Activated Protein Kinase ◽  
Mucosal Inflammation ◽  
Knock Out

Abstract Background Macrophage-inducible C-type lectin [Mincle] signalling plays a proinflammatory role in different organs such as the brain and liver, but its role in intestinal inflammation, including Crohn’s disease [CD], remains unknown. Methods The characteristics of Mincle signalling expression in CD patients and experimental colitis were examined. The functional role of Mincle signalling in the intestine was addressed in experimental colitis models in vivo by using Mincle knock-out [Mincle-/-] mice. In addition, neutralising anti-Mincle antibody, downstream spleen tyrosine kinase [Syk] inhibitor, and Mincle pharmacological agonist were used to study the Mincle signalling in intestine. Bone marrow-derived macrophages were collected from mice and used to further verify the effect of Mincle signalling in macrophages. Results This study has shown that Mincle signalling was significantly elevated in active human CD and experimental colitis, and macrophages were the principal leukocyte subset that upregulate Mincle signalling. Mincle deficiency and Syk pharmacological inhibition ameliorated the colitis by reducing induced macrophage pyroptosis, and activation of Mincle with the agonist aggravated the intestinal inflammation. The ex vivo studies demonstrated that activation of Mincle signalling promoted the release of proinflammatory cytokines, whereas its absence restricted release of proinflammatory cytokines from pyroptosis of macrophages. In addition, Mincle/Syk signalling in macrophages could promote the production of chemokines to recruit neutrophils by activating mitogen-activated protein kinase [MAPK] during intestinal inflammation. Conclusions Mincle signalling promotes intestinal mucosal inflammation by inducing macrophage pyroptosis. Modulation of the Mincle/Syk axis emerges as a potential therapeutic strategy to target inflammation and treat CD.

Experimental Intestinal Stenosis Alters Crohn’s Disease-Like Intestinal Inflammation in Ileitis-Prone Mice

2021 ◽  
Author(s):  
Ioannis Georgopoulos ◽  
Eleftheria Mavrigiannaki ◽  
Sotiria Stasinopoulou ◽  
Georgios Renieris ◽  
Georgios Nikolakis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Intestinal Stenosis

scholarly journals Dysbiosis of Gut Fungal Microbiota is Associated With Mucosal Inflammation in Crohn’s Disease

2014 ◽  
Vol 48 (6) ◽  
pp. 513-523 ◽  
Author(s):  
Qiurong Li ◽  
Chenyang Wang ◽  
Chun Tang ◽  
Qin He ◽  
Ning Li ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Inflammation ◽  
Fungal Microbiota

scholarly journals Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Fan Zhao ◽  
Tao Zheng ◽  
Wenbin Gong ◽  
Jie Wu ◽  
Haohao Xie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extracellular Vesicles ◽  
Intestinal Inflammation ◽  
Therapeutic Effects ◽  
Murine Colitis ◽  
Sting Pathway ◽  
Deficient Mice

AbstractCrohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

scholarly journals Nutritional Therapy Strategies in Pediatric Crohn’s Disease

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 212
Author(s):  
Charlotte M. Verburgt ◽  
Mohammed Ghiboub ◽  
Marc A. Benninga ◽  
Wouter J. de Jonge ◽  
Johan E. Van Limbergen
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Intestinal Inflammation ◽  
Management Strategies ◽  
Nutritional Therapy ◽  
Nutritional Deficiencies ◽  
Intestinal Immunity ◽  
Exclusive Enteral Nutrition ◽  
Therapy Strategies

The increase in incidences of pediatric Crohn’s Disease (CD) worldwide has been strongly linked with dietary shifts towards a Westernized diet, ultimately leading to altered gut microbiota and disturbance in intestinal immunity and the metabolome. Multiple clinical studies in children with CD have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission with an excellent safety profile. However, EEN is poorly tolerated, limiting its compliance and clinical application. This has spiked an interest in the development of alternative and better-tolerated nutritional therapy strategies. Several nutritional therapies have now been designed not only to treat the nutritional deficiencies seen in children with active CD but also to correct dysbiosis and reduce intestinal inflammation. In this review, we report the most recent insights regarding nutritional strategies in children with active CD: EEN, partial enteral nutrition (PEN), Crohn’s disease exclusion diet (CDED), and CD treatment-with-eating diet (CD-TREAT). We describe their setup, efficacy, safety, and (dis)advantages as well as some of their potential mechanisms of action and perspectives. A better understanding of different nutritional therapeutic options and their mechanisms will yield better and safer management strategies for children with CD and may address the barriers and limitations of current strategies in children.

Enteral nutrition for pediatric Crohn’s disease: significance and basic principles

2021 ◽  
Vol 19 (3) ◽  
pp. 70-82
Author(s):  
T.E.Borovik T.E.Borovik ◽  
◽  
A.S.Potapov A.S.Potapov ◽  
E.A.Roslavtseva E.A.Roslavtseva ◽  
A.I.Khavkin A.I.Khavkin ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Nutritional Support ◽  
Intestinal Inflammation ◽  
Bone Mineralization ◽  
Standard Diet ◽  
Newly Diagnosed ◽  
Basic Principles ◽  
Inflammatory Bowel

The characteristics of the diet traditionally recommended for Crohn’s disease often reduce patients’ consumption of essential nutrients. Therefore, an important role belongs to nutritional support with specialized formulas, the effectiveness of which has been proven both for inducing remission and optimizing the parameters of physical development and puberty, bone mineralization. Nutritional support should be provided for patients with newly diagnosed Crohn’s disease in the form of full enteral nutrition, and subsequently in remission, exacerbation, in the pre- and postoperative periods as an addition to the standard diet. Of particular interest is the CDED ModuLife program, which is based on a combination of enteral nutrition with specially selected foods aimed at reducing the activity of intestinal inflammation in Crohn’s disease. Key words: inflammatory bowel disease, Crohn’s disease, full enteral nutrition, partial enteral nutrition, enteral nutrition formulas

Sign in / Sign up

Export Citation Format

Share Document