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Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause significant small bowel injuries. The role of gut microbiota in this NSAID-induced enteropathy is poorly understood. We studied the dynamic changes in gut microbiota following indomethacin administration in mice, and investigated the effects o...

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Autores principales: Xiao, Xue, Nakatsu, Geicho, Jin, Ye, Wong, Sunny, Yu, Jun, Lau, James Y. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220306/
https://www.ncbi.nlm.nih.gov/pubmed/28067296
http://dx.doi.org/10.1038/srep40317
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author Xiao, Xue
Nakatsu, Geicho
Jin, Ye
Wong, Sunny
Yu, Jun
Lau, James Y. W.
author_facet Xiao, Xue
Nakatsu, Geicho
Jin, Ye
Wong, Sunny
Yu, Jun
Lau, James Y. W.
author_sort Xiao, Xue
collection PubMed
description Non-steroidal anti-inflammatory drugs (NSAIDs) can cause significant small bowel injuries. The role of gut microbiota in this NSAID-induced enteropathy is poorly understood. We studied the dynamic changes in gut microbiota following indomethacin administration in mice, and investigated the effects of these adaptive changes on subsequent NSAID-induced enteropathy. The changes in gut microbiota were studied using 16S rRNA sequencing, and the effects of such changes were investigated using antibiotics and a faecal transplantation model. After indomethacin treatment, significant adaptive changes in gut microbiota were observed, including increased abundance of Firmicutes and decreased abundance in that of Bacteroidetes. Depletion of gut microbiota with antibiotics led to a higher mortality (P = 0.0021) in mice compared to controls. Mice pre-transplanted with adaptively changed microbiota showed less small bowel injury and lower levels of pro-inflammatory cytokines when exposed to indomethacin. In summary, this study identifies adaptive changes in the gut microbiota upon indomethacin administration, which can in turn ameliorate further NSAID-induced injury. The heightened mortality with antibiotic depletion of the adaptively changed microbiota suggests its important role in protecting against such injury. This study provides insight for future efforts to target the microbiota as a therapeutic strategy.
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spelling pubmed-52203062017-01-11 Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin Xiao, Xue Nakatsu, Geicho Jin, Ye Wong, Sunny Yu, Jun Lau, James Y. W. Sci Rep Article Non-steroidal anti-inflammatory drugs (NSAIDs) can cause significant small bowel injuries. The role of gut microbiota in this NSAID-induced enteropathy is poorly understood. We studied the dynamic changes in gut microbiota following indomethacin administration in mice, and investigated the effects of these adaptive changes on subsequent NSAID-induced enteropathy. The changes in gut microbiota were studied using 16S rRNA sequencing, and the effects of such changes were investigated using antibiotics and a faecal transplantation model. After indomethacin treatment, significant adaptive changes in gut microbiota were observed, including increased abundance of Firmicutes and decreased abundance in that of Bacteroidetes. Depletion of gut microbiota with antibiotics led to a higher mortality (P = 0.0021) in mice compared to controls. Mice pre-transplanted with adaptively changed microbiota showed less small bowel injury and lower levels of pro-inflammatory cytokines when exposed to indomethacin. In summary, this study identifies adaptive changes in the gut microbiota upon indomethacin administration, which can in turn ameliorate further NSAID-induced injury. The heightened mortality with antibiotic depletion of the adaptively changed microbiota suggests its important role in protecting against such injury. This study provides insight for future efforts to target the microbiota as a therapeutic strategy. Nature Publishing Group 2017-01-09 /pmc/articles/PMC5220306/ /pubmed/28067296 http://dx.doi.org/10.1038/srep40317 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Xiao, Xue
Nakatsu, Geicho
Jin, Ye
Wong, Sunny
Yu, Jun
Lau, James Y. W.
Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin
title Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin
title_full Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin
title_fullStr Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin
title_full_unstemmed Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin
title_short Gut Microbiota Mediates Protection Against Enteropathy Induced by Indomethacin
title_sort gut microbiota mediates protection against enteropathy induced by indomethacin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220306/
https://www.ncbi.nlm.nih.gov/pubmed/28067296
http://dx.doi.org/10.1038/srep40317
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