2. Academic Validation
  3. Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

  • Cells. 2019 Mar 15;8(3):251. doi: 10.3390/cells8030251.
Bernadette Lázár 1,  Gábor B Brenner 2,  András Makkos 3,  Mihály Balogh 4,  Szilvia B László 5,  Mahmoud Al-Khrasani 6,  Barbara Hutka 7,  Emese Bató 8,  Eszter Ostorházi 9,  János Juhász 10,  Ágnes Kemény 11 12,  Terézia László 13,  László Tiszlavicz 14,  Zoltán Bihari 15,  Zoltán Giricz 16,  Dóra Szabó 17,  Zsuzsanna Helyes 18,  Péter Ferdinandy 19 20,  Klára Gyires 21,  Zoltán S Zádori 22
Affiliations

Affiliations

  • 1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 2 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 3 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 4 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 5 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 6 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 7 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 8 Second Department of Internal Medicine and Cardiology Center, University of Szeged, 6725 Szeged, Hungary. [email protected].
  • 9 Institute of Medical Microbiology, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 10 Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, 1083 Budapest, Hungary. [email protected].
  • 11 Department of Medical Biology, University of Pécs, 7624 Pécs, Hungary. [email protected].
  • 12 Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary. [email protected].
  • 13 Department of Pathology, University of Pécs, 7624 Pécs, Hungary. [email protected].
  • 14 Department of Pathology, University of Szeged, 6725 Szeged, Hungary. [email protected].
  • 15 Xenovea Ltd., 6726 Szeged, Hungary. [email protected].
  • 16 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 17 Institute of Medical Microbiology, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 18 Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary. [email protected].
  • 19 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 20 Pharmahungary Group, 6722 Szeged, Hungary. [email protected].
  • 21 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
  • 22 Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary. [email protected].
PMID: 30884758 DOI: 10.3390/cells8030251
Abstract

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.

Keywords

cyclooxygenase-2; enteropathy; inflammatory bowel diseases; intestinal dysbiosis; microbiota; rofecoxib.

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