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Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection
Clostridioides difficile is a major causative pathogen of nosocomial antibiotic-associated diarrhea and severe colitis. Despite the use of vancomycin and fidaxomicin as standard drugs for the treatment of C. difficile infection (CDI), clinical relapse rates remain high. Therefore, new alternative th...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691888/ https://www.ncbi.nlm.nih.gov/pubmed/36439832 http://dx.doi.org/10.3389/fmicb.2022.986457 |
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author | Lai, Yi-Hsin Wu, Tai-Chieh Tsai, Bo-Yang Hung, Yuan-Pin Lin, Hsiao-Ju Tsai, Yau-Sheng Ko, Wen-Chien Tsai, Pei-Jane |
author_facet | Lai, Yi-Hsin Wu, Tai-Chieh Tsai, Bo-Yang Hung, Yuan-Pin Lin, Hsiao-Ju Tsai, Yau-Sheng Ko, Wen-Chien Tsai, Pei-Jane |
author_sort | Lai, Yi-Hsin |
collection | PubMed |
description | Clostridioides difficile is a major causative pathogen of nosocomial antibiotic-associated diarrhea and severe colitis. Despite the use of vancomycin and fidaxomicin as standard drugs for the treatment of C. difficile infection (CDI), clinical relapse rates remain high. Therefore, new alternative therapeutics to treat CDI are urgently required. The nuclear receptor, peroxisome proliferator-activated receptor-γ (PPAR-γ), is mainly expressed in the adipose tissue and modulates lipid metabolism and insulin sensitization. Previous studies have shown that PPAR-γ is highly expressed in colonic tissues and regulates tight junction function in epithelial cells. However, the role of PPAR-γ in CDI pathogenesis remains unclear. In this study, we used a mouse model of CDI and found that both expression levels of PPAR-γ and the tight junction protein, occludin, were decreased in colonic tissues. Furthermore, to investigate the role of PPAR-γ in CDI, we used PPAR-γ defective mice and found that intestinal permeability and bacterial dissemination in these mice were significantly higher than those in wild-type mice during CDI. Administration of the PPAR-γ agonist, pioglitazone, to activate PPAR-γ activity improved the phenotypes of CDI, including bodyweight loss, inflammation, and intestinal integrity. Taken together, these results demonstrate that PPAR-γ is a potential therapeutic target in CDI, as it modulates colonic inflammation and integrity. |
format | Online Article Text |
id | pubmed-9691888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96918882022-11-26 Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection Lai, Yi-Hsin Wu, Tai-Chieh Tsai, Bo-Yang Hung, Yuan-Pin Lin, Hsiao-Ju Tsai, Yau-Sheng Ko, Wen-Chien Tsai, Pei-Jane Front Microbiol Microbiology Clostridioides difficile is a major causative pathogen of nosocomial antibiotic-associated diarrhea and severe colitis. Despite the use of vancomycin and fidaxomicin as standard drugs for the treatment of C. difficile infection (CDI), clinical relapse rates remain high. Therefore, new alternative therapeutics to treat CDI are urgently required. The nuclear receptor, peroxisome proliferator-activated receptor-γ (PPAR-γ), is mainly expressed in the adipose tissue and modulates lipid metabolism and insulin sensitization. Previous studies have shown that PPAR-γ is highly expressed in colonic tissues and regulates tight junction function in epithelial cells. However, the role of PPAR-γ in CDI pathogenesis remains unclear. In this study, we used a mouse model of CDI and found that both expression levels of PPAR-γ and the tight junction protein, occludin, were decreased in colonic tissues. Furthermore, to investigate the role of PPAR-γ in CDI, we used PPAR-γ defective mice and found that intestinal permeability and bacterial dissemination in these mice were significantly higher than those in wild-type mice during CDI. Administration of the PPAR-γ agonist, pioglitazone, to activate PPAR-γ activity improved the phenotypes of CDI, including bodyweight loss, inflammation, and intestinal integrity. Taken together, these results demonstrate that PPAR-γ is a potential therapeutic target in CDI, as it modulates colonic inflammation and integrity. Frontiers Media S.A. 2022-11-11 /pmc/articles/PMC9691888/ /pubmed/36439832 http://dx.doi.org/10.3389/fmicb.2022.986457 Text en Copyright © 2022 Lai, Wu, Tsai, Hung, Lin, Tsai, Ko and Tsai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Lai, Yi-Hsin Wu, Tai-Chieh Tsai, Bo-Yang Hung, Yuan-Pin Lin, Hsiao-Ju Tsai, Yau-Sheng Ko, Wen-Chien Tsai, Pei-Jane Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection |
title | Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection |
title_full | Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection |
title_fullStr | Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection |
title_full_unstemmed | Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection |
title_short | Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection |
title_sort | peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in clostridioides difficile infection |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691888/ https://www.ncbi.nlm.nih.gov/pubmed/36439832 http://dx.doi.org/10.3389/fmicb.2022.986457 |
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