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.
Highlights
Over the past decade, it has become increasingly recognized that nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most commonly used medications worldwide [1], both damage the stomach and duodenum and injure the lower parts of the gastrointestinal (GI) tract
This study demonstrates for the first time that long-term selective inhibition of COX-2 by rofecoxib, a compound lacking direct antibacterial and mucosal damaging properties, does not cause small intestinal dysbiosis in rats
These findings suggest that microbial alterations, reported sporadically after repeated administration of some coxibs in different species, cannot be explained by inhibition of COX-2 activity and other drug-specific properties may largely contribute
Summary
It has become increasingly recognized that nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most commonly used medications worldwide [1], both damage the stomach and duodenum and injure the lower parts of the gastrointestinal (GI) tract. Since the recognition of NSAID-induced enteropathy, much effort has been put into understanding its pathogenesis and several contributing factors have been identified [6,7,8,9]. One of these factors is the suppression of cyclooxygenase (COX)-mediated prostaglandin (PG) synthesis. According to the original expectations, these drugs produce less gastroduodenal damage than the nonselective
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