scholarly journals GPR35 in Intestinal Diseases: From Risk Gene to Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Berna Kaya ◽  
Hassan Melhem ◽  
Jan Hendrik Niess
Keyword(s):  
Cell Function ◽  
Metabolic System ◽  
Intestinal Diseases ◽  
Host Immune Responses ◽  
Risk Gene ◽  
Class A ◽  
Risk Variants ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
G Protein Coupled

Diet and gut microbial metabolites mediate host immune responses and are central to the maintenance of intestinal health. The metabolite-sensing G-protein coupled receptors (GPCRs) bind metabolites and trigger signals that are important for the host cell function, survival, proliferation and expansion. On the contrary, inadequate signaling of these metabolite-sensing GPCRs most likely participate to the development of diseases including inflammatory bowel diseases (IBD). In the intestine, metabolite-sensing GPCRs are highly expressed by epithelial cells and by specific subsets of immune cells. Such receptors provide an important link between immune system, gut microbiota and metabolic system. Member of these receptors, GPR35, a class A rhodopsin-like GPCR, has been shown to be activated by the metabolites tryptophan-derived kynurenic acid (KYNA), the chemokine CXCL17 and phospholipid derivate lysophosphatidic acid (LPA) species. There have been studies on GPR35 in the context of intestinal diseases since its identification as a risk gene for IBD. In this review, we discuss the pharmacology of GPR35 including its proposed endogenous and synthetic ligands as well as its antagonists. We elaborate on the risk variants of GPR35 implicated in gut-related diseases and the mechanisms by which GPR35 contribute to intestinal homeostasis.

scholarly journals Potential Application of Probiotics in the Prevention and Treatment of Inflammatory Bowel Diseases

Ulcers ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Silvina del Carmen ◽  
Alejandra de Moreno de LeBlanc ◽  
Anderson Miyoshi ◽  
Clarissa Santos Rocha ◽  
Vasco Azevedo ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Antioxidant Properties ◽  
Genetically Engineered ◽  
Treatment Protocols ◽  
Host Immune Responses ◽  
Beneficial Effects ◽  
Wide Range ◽  
Prevention And Treatment ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of inflammatory bowel diseases. These include changes in the gut microbiota, stimulation of the host immune responses, and reduction of the oxidative stress due to their antioxidant properties. A brief overview of the uses of genetically engineered LAB that produce either antioxidant enzymes (such as catalase and superoxide dismutase) or anti-inflammatory cytokines (such as IL-10) will also be discussed. This paper will show that probiotics should be considered in treatment protocols of IBD since they provide many beneficial effects and can enhance the effectiveness of traditional used medicines.

Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances

Gut ◽  
2019 ◽  
Vol 68 (9) ◽  
pp. 1688-1700 ◽  
Author(s):  
Sebastian Zundler ◽  
Emily Becker ◽  
Lisa Lou Schulze ◽  
Markus F Neurath
Keyword(s):  
Immune Cell ◽  
Cell Trafficking ◽  
T Cell Trafficking ◽  
Immune Cell Trafficking ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
G Protein Coupled ◽  
Lymphocyte Populations

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4β7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-β7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.

scholarly journals Uso de probióticos na nutrição de cães com Doença Inflamatória Intestinal (DII) – uma atualização

2021 ◽  
Vol 4 (5) ◽  
pp. 75-87
Author(s):  
Cláudio Marcos Rocha-de-Souza ◽  
◽  
Ana Carolina Aor Zaqueu ◽  
Lívia Rodrigues da Cruz ◽  
Marcelo Gomes de Souza ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Antibiotic Therapy ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Immunosuppressive Drugs ◽  
Intestinal Diseases ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Digestive Disorders

Canine Inflammatory Bowel Disease (IBD) is the term used to designate a group of chronic intestinal diseases, manifested by persistent or recurrent gastrointestinal signs. Known symptoms are vomiting, diarrhea, changes in appetite and weight loss. Treatment consists of a diet combined with antibiotic therapy and immunosuppressive drugs. It is currently known that changes in the microbiota profile can be used as way to prevent digestive disorders, since some probiotics offer benefits to patients with IBD, reducing symptoms and improving their immunity, however, can say that there is still no consensus regarding the recommendation of the use probiotics in inflammatory bowel diseases.

scholarly journals G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Annemarie Boleij ◽  
Payam Fathi ◽  
William Dalton ◽  
Ben Park ◽  
Xinqun Wu ◽  
...  
Keyword(s):  
G Protein ◽  
Bacteroides Fragilis ◽  
Rapid Onset ◽  
G Protein Coupled Receptor ◽  
Knock Out ◽  
Bowel Diseases ◽  
Important Virulence Factor ◽  
Inflammatory Bowel ◽  
Gastro Intestinal Tract ◽  
G Protein Coupled

AbstractG protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon.

scholarly journals Pro- and synbiotics in the treatment of intestinal diseases: what effects can we expect?

2020 ◽  
Vol 22 (12) ◽  
pp. 37-43
Author(s):  
Olga V. Gaus ◽  
◽  
Maria A. Livzan ◽  
Keyword(s):  
Clinical Practice ◽  
Digestive Tract ◽  
Diagnostic Methods ◽  
Intestinal Diseases ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Relationship ◽  
Selection Of ◽  
Real Clinical Practice

The relationship between intestinal microbiota and human health is widely recognized. The advent of molecular and genetic diagnostic methods has made it po-ssible to make truly revolutionary discoveries in the field of understanding the role of the digestive tract microbiome. Many studies have proved the association of the composition of microbiota with the development of a number of diseases of the digestive tract, such as inflammatory bowel diseases, functional gastroin-testinal disorders and some types of cancer. The food and pharmaceutical industry has presented a huge selection of food products, dietary supplements and medicines containing prebiotic and probiotic components. The use of agents that affect microbiota in the treatment of intestinal diseases in real clinical practice should be carried out strictly in accordance with the indications, in recommended doses.

P145 MECHANISMS OF ACTION FOR THE IBD-RISK GENE C1ORF106/INAVA

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Phi Luong ◽  
Wayne Lencer ◽  
Denis Chang ◽  
Qian Li
Keyword(s):  
Association Studies ◽  
Actin Dynamics ◽  
Genome Wide Association Studies ◽  
Epithelial Barrier Function ◽  
Risk Gene ◽  
Genome Wide ◽  
Bowel Diseases ◽  
Domain Of Unknown Function ◽  
Small Molecule Screen ◽  
Inflammatory Bowel

Abstract C1ORF106, also named INAVA (Innate Immune Activator), was identified as a risk gene for the chronic inflammatory bowel diseases (IBD) by genome-wide association studies and targeted exome sequencing. INAVA is highly enriched in polarized simple epithelia, the cell type that lines the intestine and interfaces most directly with the outside world. We discover that INAVA provides a direct mechanistic link between mucosal barriers and inflammation. This is driven by INAVA’s signature Domain of Unknown Function DUF3338, which we newly defined as an enhancer of IL-1β-TRAF6 polyubiquitination cascades. Our work shows that DUF3338 stably binds the GTP-exchange factor cytohesin-2 (ARNO), in one case blocking the formation of INAVA stress puncta and its effect on ubiquitination, and in another case acting at lateral membranes where the INAVA-ARNO complex regulates cortical F-actin dynamics and epithelial barrier function. We thus rename the DUF3338 domain CUPID for Cytohesin Ubiquitin Protein Inducing Domain. We performed a high throughput small molecule screen to identify molecules that modulated INAVA function in cells. Compounds hits identified in the screen links INAVA’s role in barrier and stress response mechanisms involving actin dynamics and proteostasis.

scholarly journals GLP-1 and Intestinal Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 383
Author(s):  
Jenna Elizabeth Hunt ◽  
Jens Juul Holst ◽  
Palle Bekker Jeppesen ◽  
Hannelouise Kissow
Keyword(s):  
Current Knowledge ◽  
Intestinal Diseases ◽  
Experimental Animals ◽  
New Novel ◽  
Novel Treatment ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Small Clinical Trials

Accumulating evidence implicates glucagon-like peptide-1 (GLP-1) to have, beyond glucose maintenance, a beneficial role in the gastrointestinal tract. Here, we review emerging data investigating GLP-1 as a novel treatment for intestinal diseases, including inflammatory bowel diseases, short-bowel syndrome, intestinal toxicities and coeliac disease. Possible beneficial mechanisms for these diseases include GLP-1′s influence on gastric emptying, its anti-inflammatory properties and its intestinotrophic effect. The current knowledge basis derives from the available GLP-1 agonist treatments in experimental animals and small clinical trials. However, new novel strategies including dual GLP-1/GLP-2 agonists are also in development for the treatment of intestinal diseases.

Evaluation and Treatment of Monogenic Forms of Inflammatory Bowel Diseases

2018 ◽  
Author(s):  
Dror S Shouval
Keyword(s):  
Epithelial Cell ◽  
Inflammatory Bowel Diseases ◽  
Environmental Changes ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Complex Disorders ◽  
Monogenic Disorders ◽  
Microbial Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are complex disorders that develop in genetically susceptible hosts due to dysregulated immune responses to microbial dysbiosis and environmental changes. Although in the vast majority of cases, the genetic contribution to development of these diseases is small, in rare cases, IBD develops directly as a result of deleterious mutations in the genes involved in immune and epithelial cell function. In these cases, intestinal inflammation is usually severe, which develops in most cases in the first years of life and occasionally is accompanied by recurrent or atypical infections. In this review, the approach to different monogenic disorders that cause IBD is discussed, including mutations in the IL-10 pathway, neutrophil defects, regulatory T-cell disorders, autoinflammatory conditions, epithelial cell diseases, and disorders affecting B- and T-lymphocyte dysfunction. Moreover, a multidisciplinary diagnostic approach is suggested, which highlights in which cases a monogenic disorder should be suspected. This review contains 3 figures, 3 tables, and 42 references. Key Words: inflammatory bowel disease, IL-10, chronic granulomatous disease, common variable immune deficiency, epithelial cells, genetics, immune cells, mucosal homeostasis, pathogenesis, very early–onset disease.

Evaluation and Treatment of Monogenic Forms of Inflammatory Bowel Diseases

2018 ◽  
Author(s):  
Dror S Shouval
Keyword(s):  
Epithelial Cell ◽  
Inflammatory Bowel Diseases ◽  
Environmental Changes ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Complex Disorders ◽  
Monogenic Disorders ◽  
Microbial Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are complex disorders that develop in genetically susceptible hosts due to dysregulated immune responses to microbial dysbiosis and environmental changes. Although in the vast majority of cases, the genetic contribution to development of these diseases is small, in rare cases, IBD develops directly as a result of deleterious mutations in the genes involved in immune and epithelial cell function. In these cases, intestinal inflammation is usually severe, which develops in most cases in the first years of life and occasionally is accompanied by recurrent or atypical infections. In this review, the approach to different monogenic disorders that cause IBD is discussed, including mutations in the IL-10 pathway, neutrophil defects, regulatory T-cell disorders, autoinflammatory conditions, epithelial cell diseases, and disorders affecting B- and T-lymphocyte dysfunction. Moreover, a multidisciplinary diagnostic approach is suggested, which highlights in which cases a monogenic disorder should be suspected. This review contains 3 figures, 3 tables, and 42 references. Key Words: inflammatory bowel disease, IL-10, chronic granulomatous disease, common variable immune deficiency, epithelial cells, genetics, immune cells, mucosal homeostasis, pathogenesis, very early–onset disease.

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