PhD Scientific Days 2025

Pharmaceutical Sciences and Health Technologies II.

The Selective Cyclooxygenase-2 Inhibitor Etoricoxib Causes Dysbiosis in the Rat

Name of the presenter

Zsidai Anna

Institute/workplace of the presenter

Semmelweis University, Department of Pharmacology and Pharmacotherapy

Authors

Anna Zsidai¹, Zsuzsanna Demeter¹, Arezoo Haghighi¹, Gerda Wachtl¹, Eszter Ostorházi², Dóra Szabó², Klára Gyires¹, Zoltán Zádori¹

1: Semmelweis University, Department of Pharmacology and Pharmacotherapy; Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary
2: Semmelweis University, Institute of Medical Microbiology

Text of the abstract

Introduction: In addition to genetic and environmental factors, alterations in the composition of the gut microbiota (dysbiosis) are also thought to be involved in the complex pathogenesis of rheumatoid arthritis (RA). Several gut bacterial proportions are altered in RA, many of which correlate with disease severity. Many RA patients take regularly non-steroidal anti-inflammatory drugs (NSAIDs) to relieve pain and inflammation, but these can cause stomach and intestinal damage and dysbiosis. The selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) cause less gastrointestinal damage, but little is known about their effects on the gut microbiota.
Aim: We aimed to assess the effects of celecoxib and etoricoxib, which are also used for the symptomatic treatment of RA, on the small and large intestinal microbiota in the rat.
Methods: Male Wistar rats were treated once daily per os with celecoxib (30 mg/kg), etoricoxib (10 mg/kg) or vehicle (1% hydroxyethylcellulose) for 4 weeks. At the end of the experiment, we assessed the extent of intestinal inflammation by measuring tissue levels of myeloperoxidase (MPO) and COX-2 proteins and the composition of the small and large intestinal microbiota by 16S rRNA gene sequencing. In addition, the effects of the two compounds on the growth of 12 bacteria were investigated in vitro.
Results: Neither compound increased tissue levels of MPO and COX-2, but the small intestine of etoricoxib-treated animals was significantly shortened. Treatment with celecoxib did not cause dysbiosis, whereas treatment with etoricoxib decreased the proportion of the class Clostridia in the small intestine and increased the proportion of the genus Parabacteroides and the family Tannerellaceae in the large intestine. At higher concentrations both compounds inhibited the growth of some Gram-positive bacteria in vitro.
Conclusions: Celecoxib caused neither enteritis nor dysbiosis despite inhibiting the growth of some bacteria in vitro. In contrast, chronic administration of etoricoxib caused dysbiosis in treated animals. This was associated with an increase in levels of bacteria (Parabacteroides) that have been associated with the severity of RA. These suggest that the use of etoricoxib may have a detrimental effect on the gut microbiota composition in RA, but further studies are needed to confirm this.
Grant: NKFI FK 138842