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

Bernadette Lazar, Gabor B. Brenner, Andras Makkos, Mihaly Balogh, Szilvia B. Laszlo, Mahmoud Al-Khrasani, Barbara Hutka, Emese Bato, Eszter Ostorhazi, Janos Juhasz, Agnes Kemeny, Terezia Laszlo, Laszlo Tiszlavicz, Zoltan Bihari, Zoltan Giricz, Dora Szabo, Zsuzsanna Helyes, Peter Ferdinandy, Klara Gyires, Zoltan S. Zadori*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Article number251
Number of pages17
JournalCells
Volume8
Issue number3
DOIs
Publication statusPublished - 15-Mar-2019
Externally publishedYes

Keywords

  • microbiota
  • intestinal dysbiosis
  • inflammatory bowel diseases
  • cyclooxygenase-2
  • rofecoxib
  • enteropathy
  • NONSTEROIDAL ANTIINFLAMMATORY DRUGS
  • INFLAMMATORY-BOWEL-DISEASE
  • PROTON PUMP INHIBITORS
  • GASTROINTESTINAL TOXICITY
  • RHEUMATOID-ARTHRITIS
  • NSAID ENTEROPATHY
  • MECHANISMS
  • MICROBIOTA
  • CELECOXIB
  • DAMAGE

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