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Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS

Both mast cells and microbiota play important roles in the pathogenesis of Irritable Bowel Syndrome (IBS), however the precise mechanisms are unknown. Using microbiota-humanized IBS mouse model, we show that colonic mast cells and mast cells co-localized with neurons were higher in mice colonized wi...

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Autores principales: Shimbori, Chiko, De Palma, Giada, Baerg, Lauren, Lu, Jun, Verdu, Elena F., Reed, David E., Vanner, Stephen, Collins, Stephen M., Bercik, Premysl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341375/
https://www.ncbi.nlm.nih.gov/pubmed/35905313
http://dx.doi.org/10.1080/19490976.2022.2105095
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author Shimbori, Chiko
De Palma, Giada
Baerg, Lauren
Lu, Jun
Verdu, Elena F.
Reed, David E.
Vanner, Stephen
Collins, Stephen M.
Bercik, Premysl
author_facet Shimbori, Chiko
De Palma, Giada
Baerg, Lauren
Lu, Jun
Verdu, Elena F.
Reed, David E.
Vanner, Stephen
Collins, Stephen M.
Bercik, Premysl
author_sort Shimbori, Chiko
collection PubMed
description Both mast cells and microbiota play important roles in the pathogenesis of Irritable Bowel Syndrome (IBS), however the precise mechanisms are unknown. Using microbiota-humanized IBS mouse model, we show that colonic mast cells and mast cells co-localized with neurons were higher in mice colonized with IBS microbiota compared with those with healthy control (HC) microbiota. In situ hybridization showed presence of IBS, but not control microbiota, in the lamina propria and RNAscope demonstrated frequent co-localization of IBS bacteria and mast cells. TLR4 and H(4) receptor expression was higher in mice with IBS microbiota, and in peritoneal-derived and bone marrow-derived mast cells (BMMCs) stimulated with IBS bacterial supernatant, which also increased BMMCs degranulation, chemotaxis, adherence and histamine release. While both TLR4 and H(4) receptor inhibitors prevented BMMCs degranulation, only the latter attenuated their chemotaxis. We provide novel insights into the mechanisms, which contribute to gut dysfunction and visceral hypersensitivity in IBS.
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spelling pubmed-93413752022-08-02 Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS Shimbori, Chiko De Palma, Giada Baerg, Lauren Lu, Jun Verdu, Elena F. Reed, David E. Vanner, Stephen Collins, Stephen M. Bercik, Premysl Gut Microbes Report Both mast cells and microbiota play important roles in the pathogenesis of Irritable Bowel Syndrome (IBS), however the precise mechanisms are unknown. Using microbiota-humanized IBS mouse model, we show that colonic mast cells and mast cells co-localized with neurons were higher in mice colonized with IBS microbiota compared with those with healthy control (HC) microbiota. In situ hybridization showed presence of IBS, but not control microbiota, in the lamina propria and RNAscope demonstrated frequent co-localization of IBS bacteria and mast cells. TLR4 and H(4) receptor expression was higher in mice with IBS microbiota, and in peritoneal-derived and bone marrow-derived mast cells (BMMCs) stimulated with IBS bacterial supernatant, which also increased BMMCs degranulation, chemotaxis, adherence and histamine release. While both TLR4 and H(4) receptor inhibitors prevented BMMCs degranulation, only the latter attenuated their chemotaxis. We provide novel insights into the mechanisms, which contribute to gut dysfunction and visceral hypersensitivity in IBS. Taylor & Francis 2022-07-29 /pmc/articles/PMC9341375/ /pubmed/35905313 http://dx.doi.org/10.1080/19490976.2022.2105095 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Report
Shimbori, Chiko
De Palma, Giada
Baerg, Lauren
Lu, Jun
Verdu, Elena F.
Reed, David E.
Vanner, Stephen
Collins, Stephen M.
Bercik, Premysl
Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS
title Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS
title_full Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS
title_fullStr Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS
title_full_unstemmed Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS
title_short Gut bacteria interact directly with colonic mast cells in a humanized mouse model of IBS
title_sort gut bacteria interact directly with colonic mast cells in a humanized mouse model of ibs
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341375/
https://www.ncbi.nlm.nih.gov/pubmed/35905313
http://dx.doi.org/10.1080/19490976.2022.2105095
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