PhD Scientific Days 2018

Budapest, April 19–20, 2018

Long-term selective inhibition of cyclooxygenase-2 by rofecoxib does not cause small intestinal dysbiosis in the rat

László, Szilvia

Szilvia László1, Bernadette Lázár1, Gábor Brenner1, Emese Bató2, Eszter Ostorházi3, János Juhász4, Dóra Szabó3, Péter Ferdinandy1, Klára Gyires1, Zoltán S. Zádori1

1Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest
2Second Department of Internal Medicine and Cardiology Center, University of Szeged, Szeged
3Institute of Medical Microbiology, Semmelweis University, Budapest
4Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest

Language of the presentation

Hungarian

Text of the abstract

Introduction: Several lines of evidence suggest that nonsteroidal anti-inflammatory drugs do not only damage the mucosa of the gastrointestinal tract, but also alter significantly the composition of the microbiota. It is, however, still not clear whether selective cyclooxygenase-2 (COX-2) inhibitors, that are much safer for the gastrointestinal tract, have any effect on the small intestinal microbes. Although celecoxib was shown to induce dysbiosis, it also has direct antibacterial effect against Gram-positive strains, therefore its dysbiotic effect may be unrelated to COX-2 inhibition. Aims: To evaluate the effects of another selective COX-2 inhibitor, rofecoxib, 1) on the small intestinal microbiota in the rat, and 2) on the growth of distinct Gram-positive and Gram-negative bacteria in vitro. Methods: Male Wistar rats were treated with either or with its vehicle for 4 weeks. After the chronic treatment the jejunal luminal content was collected, and the composition of its microflora was determined by deep sequencing of 16S rRNA. The direct effect of rofecoxib on the growth of various bacteria was examined by the broth microdilution assay. Results: 1. Celecoxib inhibited the growth of various Gram-positive bacteria, with MICs ranging from 32-64 mg/l, whereas Gram-negative bacteria were not affected. In contrast, rofecoxib (up to 256 mg/l) had no significant inhibitory effect on the growth of any of the bacteria tested. 2. The 4-week treatment with rofecoxib did not influence significantly the abundance of the identified small intestinal organisms and had no significant effect on the diversity of microbiota. Conclusions: This study demonstrates for the first time that selective COX-2 inhibition does not influence the small intestinal microbiota, and suggests that the observed dysbiotic effect of celecoxib is due to its direct antibacterial property. The research was supported by National Research, Development and Innovation Office of Hungary (NKFI FK 124878; NVKP-16-1-2016-0017 National Heart Program).

Data of the presenter

Doctoral School: Doctoral School of Pharmaceutical Sciences
Program: Experimental and Clinical Pharmacology
Supervisor: Zoltán S. Zádori (zadori.zoltan@med.semmelweis-univ.hu)
Email: laszloszilvi91@gmail.com