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Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses

Inflammatory bowel disease (IBD) is associated with a loss of intestinal barrier function and dysregulated immune responses. It has been shown that short chain fatty acids (SCFAs) are protective in IBD and that GPR43 mediates the protective effects of SCFAs. In this study, we investigated the effect...

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Autores principales: D’Souza, Warren N., Douangpanya, Jason, Mu, Sharon, Jaeckel, Peter, Zhang, Ming, Maxwell, Joseph R., Rottman, James B., Labitzke, Katja, Willee, Angela, Beckmann, Holger, Wang, Yingcai, Li, Yang, Schwandner, Ralf, Johnston, James A., Towne, Jennifer E., Hsu, Hailing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519041/
https://www.ncbi.nlm.nih.gov/pubmed/28727837
http://dx.doi.org/10.1371/journal.pone.0180190
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author D’Souza, Warren N.
Douangpanya, Jason
Mu, Sharon
Jaeckel, Peter
Zhang, Ming
Maxwell, Joseph R.
Rottman, James B.
Labitzke, Katja
Willee, Angela
Beckmann, Holger
Wang, Yingcai
Li, Yang
Schwandner, Ralf
Johnston, James A.
Towne, Jennifer E.
Hsu, Hailing
author_facet D’Souza, Warren N.
Douangpanya, Jason
Mu, Sharon
Jaeckel, Peter
Zhang, Ming
Maxwell, Joseph R.
Rottman, James B.
Labitzke, Katja
Willee, Angela
Beckmann, Holger
Wang, Yingcai
Li, Yang
Schwandner, Ralf
Johnston, James A.
Towne, Jennifer E.
Hsu, Hailing
author_sort D’Souza, Warren N.
collection PubMed
description Inflammatory bowel disease (IBD) is associated with a loss of intestinal barrier function and dysregulated immune responses. It has been shown that short chain fatty acids (SCFAs) are protective in IBD and that GPR43 mediates the protective effects of SCFAs. In this study, we investigated the effects of SCFAs in comparison to highly specific GPR43 agonists on human intestinal epithelial and immune cells. Our results confirm that SCFAs are enhancers of barrier function in intestinal epithelial cells. Additionally, SCFAs also displayed potent immunoregulatory properties based upon the ability to inhibit LPS-induced cytokine production in PBMC, and human T cell proliferation and cytokine production. Unexpectedly, and in contrast to the current belief, specific GPR43 agonists failed to exhibit similar barrier enhancing and anti-inflammatory properties. These findings demonstrate that SCFA possess broad protective functions in IBD and agonizing GPR43 alone is unlikely to be beneficial in patients.
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spelling pubmed-55190412017-08-07 Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses D’Souza, Warren N. Douangpanya, Jason Mu, Sharon Jaeckel, Peter Zhang, Ming Maxwell, Joseph R. Rottman, James B. Labitzke, Katja Willee, Angela Beckmann, Holger Wang, Yingcai Li, Yang Schwandner, Ralf Johnston, James A. Towne, Jennifer E. Hsu, Hailing PLoS One Research Article Inflammatory bowel disease (IBD) is associated with a loss of intestinal barrier function and dysregulated immune responses. It has been shown that short chain fatty acids (SCFAs) are protective in IBD and that GPR43 mediates the protective effects of SCFAs. In this study, we investigated the effects of SCFAs in comparison to highly specific GPR43 agonists on human intestinal epithelial and immune cells. Our results confirm that SCFAs are enhancers of barrier function in intestinal epithelial cells. Additionally, SCFAs also displayed potent immunoregulatory properties based upon the ability to inhibit LPS-induced cytokine production in PBMC, and human T cell proliferation and cytokine production. Unexpectedly, and in contrast to the current belief, specific GPR43 agonists failed to exhibit similar barrier enhancing and anti-inflammatory properties. These findings demonstrate that SCFA possess broad protective functions in IBD and agonizing GPR43 alone is unlikely to be beneficial in patients. Public Library of Science 2017-07-20 /pmc/articles/PMC5519041/ /pubmed/28727837 http://dx.doi.org/10.1371/journal.pone.0180190 Text en © 2017 D’Souza et al http://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/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
D’Souza, Warren N.
Douangpanya, Jason
Mu, Sharon
Jaeckel, Peter
Zhang, Ming
Maxwell, Joseph R.
Rottman, James B.
Labitzke, Katja
Willee, Angela
Beckmann, Holger
Wang, Yingcai
Li, Yang
Schwandner, Ralf
Johnston, James A.
Towne, Jennifer E.
Hsu, Hailing
Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses
title Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses
title_full Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses
title_fullStr Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses
title_full_unstemmed Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses
title_short Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses
title_sort differing roles for short chain fatty acids and gpr43 agonism in the regulation of intestinal barrier function and immune responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519041/
https://www.ncbi.nlm.nih.gov/pubmed/28727837
http://dx.doi.org/10.1371/journal.pone.0180190
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