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Gut-derived butyrate suppresses ocular surface inflammation
Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially prod...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927112/ https://www.ncbi.nlm.nih.gov/pubmed/35296712 http://dx.doi.org/10.1038/s41598-022-08442-3 |
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author | Schaefer, Laura Hernandez, Humberto Coats, Rosalind A. Yu, Zhiyuan Pflugfelder, Stephen C. Britton, Robert A. de Paiva, Cintia S. |
author_facet | Schaefer, Laura Hernandez, Humberto Coats, Rosalind A. Yu, Zhiyuan Pflugfelder, Stephen C. Britton, Robert A. de Paiva, Cintia S. |
author_sort | Schaefer, Laura |
collection | PubMed |
description | Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of in vitro corneal epithelial cultures or bone marrow-derived dendritic cells (BMDCs) with phenylbutyrate (PBA) reduces lipopolysaccharide-induced pro-inflammatory Tnf expression. Corneal epithelial cultures and BMDCs isolated from Slc5a8 knockout mice are unable to respond to PBA pre-treatment, suggesting that SLC5A8 is required for the protective effect of PBA. The treatment of mice undergoing desiccating stress (DS) with oral tributyrin, a prodrug form of butyrate, reduces inflammation at the ocular surface in vivo, and this effect partially requires SLC5A8. Finally, expression analysis on conjunctival tissue isolated from mice subjected to DS with and without tributyrin treatment revealed that treatment downregulated genes involved in Type I interferon signaling. Together these data support our hypothesis that SCFAs produced in the gut participate in the maintenance of ocular surface homeostasis. |
format | Online Article Text |
id | pubmed-8927112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89271122022-03-17 Gut-derived butyrate suppresses ocular surface inflammation Schaefer, Laura Hernandez, Humberto Coats, Rosalind A. Yu, Zhiyuan Pflugfelder, Stephen C. Britton, Robert A. de Paiva, Cintia S. Sci Rep Article Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of in vitro corneal epithelial cultures or bone marrow-derived dendritic cells (BMDCs) with phenylbutyrate (PBA) reduces lipopolysaccharide-induced pro-inflammatory Tnf expression. Corneal epithelial cultures and BMDCs isolated from Slc5a8 knockout mice are unable to respond to PBA pre-treatment, suggesting that SLC5A8 is required for the protective effect of PBA. The treatment of mice undergoing desiccating stress (DS) with oral tributyrin, a prodrug form of butyrate, reduces inflammation at the ocular surface in vivo, and this effect partially requires SLC5A8. Finally, expression analysis on conjunctival tissue isolated from mice subjected to DS with and without tributyrin treatment revealed that treatment downregulated genes involved in Type I interferon signaling. Together these data support our hypothesis that SCFAs produced in the gut participate in the maintenance of ocular surface homeostasis. Nature Publishing Group UK 2022-03-16 /pmc/articles/PMC8927112/ /pubmed/35296712 http://dx.doi.org/10.1038/s41598-022-08442-3 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Schaefer, Laura Hernandez, Humberto Coats, Rosalind A. Yu, Zhiyuan Pflugfelder, Stephen C. Britton, Robert A. de Paiva, Cintia S. Gut-derived butyrate suppresses ocular surface inflammation |
title | Gut-derived butyrate suppresses ocular surface inflammation |
title_full | Gut-derived butyrate suppresses ocular surface inflammation |
title_fullStr | Gut-derived butyrate suppresses ocular surface inflammation |
title_full_unstemmed | Gut-derived butyrate suppresses ocular surface inflammation |
title_short | Gut-derived butyrate suppresses ocular surface inflammation |
title_sort | gut-derived butyrate suppresses ocular surface inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927112/ https://www.ncbi.nlm.nih.gov/pubmed/35296712 http://dx.doi.org/10.1038/s41598-022-08442-3 |
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