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Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling

Irritable bowel syndrome (IBS) displays chronic abdominal pain with altered defecation. Most of the patients develop visceral hypersensitivity possibly resulting from impaired gut barrier and altered gut microbiota. We previously demonstrated that colonic hyperpermeability with visceral hypersensiti...

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Detalles Bibliográficos
Autores principales: Nozu, Tsukasa, Okumura, Toshikatsu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Neurogastroenterology and Motility 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978123/
https://www.ncbi.nlm.nih.gov/pubmed/35189599
http://dx.doi.org/10.5056/jnm21002
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author Nozu, Tsukasa
Okumura, Toshikatsu
author_facet Nozu, Tsukasa
Okumura, Toshikatsu
author_sort Nozu, Tsukasa
collection PubMed
description Irritable bowel syndrome (IBS) displays chronic abdominal pain with altered defecation. Most of the patients develop visceral hypersensitivity possibly resulting from impaired gut barrier and altered gut microbiota. We previously demonstrated that colonic hyperpermeability with visceral hypersensitivity in animal IBS models, which is mediated via corticotropin-releasing factor (CRF)–Toll-like receptor 4 (TLR4)–proinflammatory cytokine signaling. CRF impairs gut barrier via TLR4. Leaky gut induces bacterial translocation resulting in dysbiosis, and increases lipopolysaccharide (LPS). Activation of TLR4 by LPS increases the production of proinflammatory cytokines, which activate visceral sensory neurons to induce visceral hypersensitivity. LPS also activates CRF receptors to further increase gut permeability. Metabolic syndrome (MS) is a cluster of cardiovascular risk factors, including insulin resistance, obesity, dyslipidemia, and hypertension, and recently several researchers suggested the possibility that impaired gut barrier and dysbiosis with low-grade systemic inflammation are involved in MS. Moreover, TLR4–proinflammatory cytokine contributes to the development of insulin resistance and obesity. Thus, the existence of pathophysiological commonality between IBS and MS is expected. This review discusses the potential mechanisms of IBS and MS with reference to gut barrier and microbiota, and explores the possibility of existence of a pathophysiological link between these diseases with a focus on CRF, TLR4, and proinflammatory cytokine signaling. We also review epidemiological data supporting this possibility, and discuss the potential of therapeutic application of the drugs used for MS to IBS treatment. This notion may pave the way for exploring novel therapeutic approaches for these disorders.
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spelling pubmed-89781232022-04-30 Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling Nozu, Tsukasa Okumura, Toshikatsu J Neurogastroenterol Motil Review Irritable bowel syndrome (IBS) displays chronic abdominal pain with altered defecation. Most of the patients develop visceral hypersensitivity possibly resulting from impaired gut barrier and altered gut microbiota. We previously demonstrated that colonic hyperpermeability with visceral hypersensitivity in animal IBS models, which is mediated via corticotropin-releasing factor (CRF)–Toll-like receptor 4 (TLR4)–proinflammatory cytokine signaling. CRF impairs gut barrier via TLR4. Leaky gut induces bacterial translocation resulting in dysbiosis, and increases lipopolysaccharide (LPS). Activation of TLR4 by LPS increases the production of proinflammatory cytokines, which activate visceral sensory neurons to induce visceral hypersensitivity. LPS also activates CRF receptors to further increase gut permeability. Metabolic syndrome (MS) is a cluster of cardiovascular risk factors, including insulin resistance, obesity, dyslipidemia, and hypertension, and recently several researchers suggested the possibility that impaired gut barrier and dysbiosis with low-grade systemic inflammation are involved in MS. Moreover, TLR4–proinflammatory cytokine contributes to the development of insulin resistance and obesity. Thus, the existence of pathophysiological commonality between IBS and MS is expected. This review discusses the potential mechanisms of IBS and MS with reference to gut barrier and microbiota, and explores the possibility of existence of a pathophysiological link between these diseases with a focus on CRF, TLR4, and proinflammatory cytokine signaling. We also review epidemiological data supporting this possibility, and discuss the potential of therapeutic application of the drugs used for MS to IBS treatment. This notion may pave the way for exploring novel therapeutic approaches for these disorders. The Korean Society of Neurogastroenterology and Motility 2022-04-30 2022-04-30 /pmc/articles/PMC8978123/ /pubmed/35189599 http://dx.doi.org/10.5056/jnm21002 Text en © 2022 The Korean Society of Neurogastroenterology and Motility https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Nozu, Tsukasa
Okumura, Toshikatsu
Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling
title Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling
title_full Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling
title_fullStr Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling
title_full_unstemmed Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling
title_short Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor–Toll-like Receptor 4–Proinflammatory Cytokine Signaling
title_sort pathophysiological commonality between irritable bowel syndrome and metabolic syndrome: role of corticotropin-releasing factor–toll-like receptor 4–proinflammatory cytokine signaling
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978123/
https://www.ncbi.nlm.nih.gov/pubmed/35189599
http://dx.doi.org/10.5056/jnm21002
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