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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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