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Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat
Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four we...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468807/ https://www.ncbi.nlm.nih.gov/pubmed/30884758 http://dx.doi.org/10.3390/cells8030251 |
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author | Lázár, Bernadette Brenner, Gábor B. Makkos, András Balogh, Mihály László, Szilvia B. Al-Khrasani, Mahmoud Hutka, Barbara Bató, Emese Ostorházi, Eszter Juhász, János Kemény, Ágnes László, Terézia Tiszlavicz, László Bihari, Zoltán Giricz, Zoltán Szabó, Dóra Helyes, Zsuzsanna Ferdinandy, Péter Gyires, Klára Zádori, Zoltán S. |
author_facet | Lázár, Bernadette Brenner, Gábor B. Makkos, András Balogh, Mihály László, Szilvia B. Al-Khrasani, Mahmoud Hutka, Barbara Bató, Emese Ostorházi, Eszter Juhász, János Kemény, Ágnes László, Terézia Tiszlavicz, László Bihari, Zoltán Giricz, Zoltán Szabó, Dóra Helyes, Zsuzsanna Ferdinandy, Péter Gyires, Klára Zádori, Zoltán S. |
author_sort | Lázár, Bernadette |
collection | PubMed |
description | Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it. |
format | Online Article Text |
id | pubmed-6468807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64688072019-04-23 Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat Lázár, Bernadette Brenner, Gábor B. Makkos, András Balogh, Mihály László, Szilvia B. Al-Khrasani, Mahmoud Hutka, Barbara Bató, Emese Ostorházi, Eszter Juhász, János Kemény, Ágnes László, Terézia Tiszlavicz, László Bihari, Zoltán Giricz, Zoltán Szabó, Dóra Helyes, Zsuzsanna Ferdinandy, Péter Gyires, Klára Zádori, Zoltán S. Cells Article Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it. MDPI 2019-03-15 /pmc/articles/PMC6468807/ /pubmed/30884758 http://dx.doi.org/10.3390/cells8030251 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lázár, Bernadette Brenner, Gábor B. Makkos, András Balogh, Mihály László, Szilvia B. Al-Khrasani, Mahmoud Hutka, Barbara Bató, Emese Ostorházi, Eszter Juhász, János Kemény, Ágnes László, Terézia Tiszlavicz, László Bihari, Zoltán Giricz, Zoltán Szabó, Dóra Helyes, Zsuzsanna Ferdinandy, Péter Gyires, Klára Zádori, Zoltán S. Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
title | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
title_full | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
title_fullStr | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
title_full_unstemmed | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
title_short | Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat |
title_sort | lack of small intestinal dysbiosis following long-term selective inhibition of cyclooxygenase-2 by rofecoxib in the rat |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468807/ https://www.ncbi.nlm.nih.gov/pubmed/30884758 http://dx.doi.org/10.3390/cells8030251 |
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