scholarly journals Metabolite-Sensing G Protein-Coupled Receptors Connect the Diet-Microbiota-Metabolites Axis to Inflammatory Bowel Disease

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 450 ◽  
Author(s):  
Hassan Melhem ◽  
Berna Kaya ◽  
C. Korcan Ayata ◽  
Petr Hruz ◽  
Jan Hendrik Niess
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune System ◽  
G Protein ◽  
Bowel Disease ◽  
Physiological Role ◽  
G Protein Coupled Receptors ◽  
Signaling Function ◽  
Function Expression ◽  
Inflammatory Bowel ◽  
G Protein Coupled

Increasing evidence has indicated that diet and metabolites, including bacteria- and host-derived metabolites, orchestrate host pathophysiology by regulating metabolism, immune system and inflammation. Indeed, autoimmune diseases such as inflammatory bowel disease (IBD) are associated with the modulation of host response to diets. One crucial mechanism by which the microbiota affects the host is signaling through G protein-coupled receptors (GPCRs) termed metabolite-sensing GPCRs. In the gut, both immune and nonimmune cells express GPCRs and their activation generally provide anti-inflammatory signals through regulation of both the immune system functions and the epithelial integrity. Members of GPCR family serve as a link between microbiota, immune system and intestinal epithelium by which all these components crucially participate to maintain the gut homeostasis. Conversely, impaired GPCR signaling is associated with IBD and other diseases, including hepatic steatosis, diabetes, cardiovascular disease, and asthma. In this review, we first outline the signaling, function, expression and the physiological role of several groups of metabolite-sensing GPCRs. We then discuss recent findings on their role in the regulation of the inflammation, their existing endogenous and synthetic ligands and innovative approaches to therapeutically target inflammatory bowel disease.

scholarly journals Roles of G protein-coupled receptors in inflammatory bowel disease

2020 ◽  
Vol 26 (12) ◽  
pp. 1242-1261
Author(s):  
Zhen Zeng ◽  
Arjudeb Mukherjee ◽  
Adwin Pidiyath Varghese ◽  
Xiao-Li Yang ◽  
Sha Chen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
G Protein ◽  
Bowel Disease ◽  
G Protein Coupled Receptors ◽  
Inflammatory Bowel ◽  
G Protein Coupled

scholarly journals P071 G protein-coupled receptor 30 expression in inflammatory bowel disease patients

2014 ◽  
Vol 8 ◽  
pp. S92 ◽  
Author(s):  
A. Sobolewska ◽  
M. Wlodarczyk ◽  
A. Piechota-Polanczyk ◽  
J. Fichna ◽  
M. Wisniewska-Jarosinska
Keyword(s):  
Inflammatory Bowel Disease ◽  
G Protein ◽  
Bowel Disease ◽  
G Protein Coupled Receptor ◽  
Inflammatory Bowel ◽  
G Protein Coupled

scholarly journals P364 New insights into the molecular mechanisms of thalidomide in paediatric inflammatory bowel disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S345-S346
Author(s):  
M Lucafò ◽  
M Bramuzzo ◽  
L Pugnetti ◽  
M Gerdol ◽  
S Greco ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
G Protein ◽  
Molecular Mechanism ◽  
Bowel Disease ◽  
Differentially Expressed ◽  
Hypergeometric Test ◽  
G Protein Coupled Receptor ◽  
Receptor Signalling ◽  
Inflammatory Bowel ◽  
G Protein Coupled

Abstract Background Thalidomide is an effective drug in children with inflammatory bowel disease (IBD) refractory to standard treatments, however, its use is often limited by its safety profile, in particular for the risk of teratogenicity and peripheral neuropathy. Multiple hypotheses exist to explain the molecular mechanism of thalidomide action but no data have been published on IBD patients. To identify determinants of thalidomide action in paediatric IBD, high-throughput microRNA (miRNA) and messenger RNAs (mRNA) profiles during treatment were analysed. Methods IBD patients responsive to thalidomide were enrolled. miRNA and mRNA profiles from peripheral blood obtained before and after 12 weeks of treatment were determined using next-generation sequencing. Differentially expressed genes were identified by fold change from the general linear model. In order to detect the potentially altered pathways, the hypergeometric test based on gene ontology annotations was used. The identification of putative mRNA targets of thalidomide sensitive miRNAs was performed by Targetscan database. Results Ten IBD paediatric patients (mean age 13.1 years, 6 males) were enrolled. Sequencing analysis identified 10 miRNAs (3 downregulated) and 252 mRNAs (76 downregulated) deregulated after treatment. Five upregulated miRNAs could putatively recognise the 3′UTR of several Hox genes, a group of transcription factors that play important roles in the development of structures such as limbs, lungs and nervous system. The hypergeometric test highlighted the altered pathways involved in inflammatory response, regulation of immune system, prostaglandin receptor activity and G protein-coupled receptor signalling. Among the 10 miRNAs deregulated by thalidomide, six could putatively regulate the differentially expressed mRNAs resulting from the analyses. Conclusion Thalidomide induces specific gene expression alterations, which could help to elucidate its molecular mechanism in paediatric IBD patients. miRNA results may suggest new molecular targets involved in the teratogenic effects of this drug. Moreover, mRNA profiles indicate a strong involvement of adenylate cyclase-modulating G protein-coupled receptor signalling in the thalidomide mechanism of action.

scholarly journals Bile Acid Signaling in Inflammatory Bowel Disease

2021 ◽  
Vol 22 (16) ◽  
pp. 9096
Author(s):  
Mariusz A. Bromke ◽  
Małgorzata Krzystek-Korpacka
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Bile Acid ◽  
Bile Acids ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Physiological Role ◽  
Membrane Receptors ◽  
Bile Acid Metabolism ◽  
Inflammatory Bowel

Inflammatory bowel disease is a chronic, idiopathic and complex condition, which most often manifests itself in the form of ulcerative colitis or Crohn’s disease. Both forms are associated with dysregulation of the mucosal immune system, compromised intestinal epithelial barrier, and dysbiosis of the gut microbiome. It has been observed for a long time that bile acids are involved in inflammatory disorders, and recent studies show their significant physiological role, reaching far beyond being emulsifiers helping in digestion of lipids. Bile acids are also signaling molecules, which act, among other things, on lipid metabolism and immune responses, through several nuclear and membrane receptors in hepatocytes, enterocytes and cells of the immune system. Gut microbiota homeostasis also seems to be affected, directly and indirectly, by bile acid metabolism and signaling. This review summarizes recent advances in the field of bile acid signaling, studies of inflamed gut microbiome, and the therapeutic potential of bile acids in the context of inflammatory bowel disease.

Natural Products: Experimental Efficient Agents for Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Natural Products ◽  
Immune System ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Receptor Protein ◽  
Intestinal Epithelia ◽  
Inflammatory Bowel ◽  
The Individual

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

scholarly journals Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease

mBio ◽  
2021 ◽  
Author(s):  
Nathaniel D. Chu ◽  
Jessica W. Crothers ◽  
Le T. T. Nguyen ◽  
Sean M. Kearney ◽  
Mark B. Smith ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Bowel Disease ◽  
Healthy Donor ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Complex Mixtures ◽  
Sick Patient ◽  
Inflammatory Bowel ◽  
Living Organisms

Fecal microbiota transplantation (FMT)—transferring fecal microbes from a healthy donor to a sick patient—has shown promise for gut diseases such as inflammatory bowel disease. However, unlike pharmaceuticals, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient.

scholarly journals Microbiota-nourishing Immunity and Its Relevance for Ulcerative Colitis

2019 ◽  
Vol 25 (5) ◽  
pp. 811-815 ◽  
Author(s):  
Mariana X Byndloss ◽  
Yael Litvak ◽  
Andreas J Bäumler
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Environmental Exposure ◽  
Large Intestine ◽  
Bowel Disease ◽  
Human Diseases ◽  
Colonization Resistance ◽  
Inflammatory Bowel ◽  
New Hypothesis

An imbalance in our microbiota may contribute to many human diseases, but the mechanistic underpinnings of dysbiosis remain poorly understood. We argue that dysbiosis is secondary to a defect in microbiota-nourishing immunity, a part of our immune system that balances the microbiota to attain colonization resistance against environmental exposure to microorganisms. We discuss this new hypothesis and its implications for ulcerative colitis, an inflammatory bowel disease of the large intestine.

scholarly journals Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

2007 ◽  
Vol 7 ◽  
pp. 1073-1081 ◽  
Author(s):  
Luigi F. Agnati ◽  
Giuseppina Leo ◽  
Susanna Genedani ◽  
Diego Guidolin ◽  
Nicola Andreoli ◽  
...  
Keyword(s):  
Immune System ◽  
G Protein ◽  
Cell Metabolism ◽  
G Protein Coupled Receptors ◽  
Host Cells ◽  
Receptor Function ◽  
Viral Receptor ◽  
Receptor Interactions ◽  
Induced Changes ◽  
G Protein Coupled

It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers), but clusters of receptors (receptor mosaics), altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

scholarly journals Inflammatory Bowel Disease: The Emergence of New Trends in Lifestyle and Nanomedicine as the Modern Tool for Pharmacotherapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2460
Author(s):  
Eden Mariam Jacob ◽  
Ankita Borah ◽  
Sindhu C Pillai ◽  
D. Sakthi Kumar
Keyword(s):  
Drug Delivery ◽  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Bowel Disease ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Genetic Defect ◽  
Delivery Systems ◽  
Conventional Drug ◽  
Inflammatory Bowel

The human intestine, which harbors trillions of symbiotic microorganisms, may enter into dysbiosis when exposed to a genetic defect or environmental stress. The naissance of chronic inflammation due to the battle of the immune system with the trespassing gut bacteria leads to the rise of inflammatory bowel disease (IBD). Though the genes behind the scenes and their link to the disease are still unclear, the onset of IBD occurs in young adults and has expanded from the Western world into the newly industrialized countries. Conventional drug deliveries depend on a daily heavy dosage of immune suppressants or anti-inflammatory drugs targeted for the treatment of two types of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), which are often associated with systemic side effects and adverse toxicities. Advances in oral delivery through nanotechnology seek remedies to overcome the drawbacks of these conventional drug delivery systems through improved drug encapsulation and targeted delivery. In this review, we discuss the association of genetic factors, the immune system, the gut microbiome, and environmental factors like diet in the pathogenesis of IBD. We also review the various physiological concerns required for oral delivery to the gastrointestinal tract (GIT) and new strategies in nanotechnology-derived, colon-targeting drug delivery systems.

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