APA
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Barekat, K., Ghosh, S., Herrmann, C., Keat, K., Assenmacher, C., Tanes, C., … Ricciotti, E. (2026). Concomitant COX-1 and COX-2 suppression is not sufficient to induce enteropathy associated with chronic NSAID use. Journal of Clinical Investigation.
Chicago/Turabian
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Barekat, Kayla, Soumita Ghosh, Christin Herrmann, Karl Keat, C. Assenmacher, Ceylan Tanes, Naomi Wilson, et al. “Concomitant COX-1 and COX-2 Suppression Is Not Sufficient to Induce Enteropathy Associated with Chronic NSAID Use.” Journal of Clinical Investigation (2026).
MLA
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Barekat, Kayla, et al. “Concomitant COX-1 and COX-2 Suppression Is Not Sufficient to Induce Enteropathy Associated with Chronic NSAID Use.” Journal of Clinical Investigation, 2026.
BibTeX Click to copy
@article{kayla2026a,
title = {Concomitant COX-1 and COX-2 suppression is not sufficient to induce enteropathy associated with chronic NSAID use.},
year = {2026},
journal = {Journal of Clinical Investigation},
author = {Barekat, Kayla and Ghosh, Soumita and Herrmann, Christin and Keat, Karl and Assenmacher, C. and Tanes, Ceylan and Wilson, Naomi and Lordan, R. and Mrcela, Antonijo and Rauova, Lubica and Sengupta, Arjun and Das, U. S. and Joshi, Robin and Friedman, E. and Ritchie, Marylyn D. and Bittinger, K. and Weljie, A. and Cadwell, Ken and Bushman, Frederic D. and Wu, Gary D. and Fitzgerald, G. and Ricciotti, E.}
}
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications for the management of chronic pain; however, they are associated with numerous gastrointestinal (GI) adverse events. Although many mechanisms have been suggested, NSAID-induced enteropathy has been thought to be primarily due to inhibition of both cyclooxygenases (COX) -1 and -2, which results in suppression of prostaglandin synthesis. Yet surprisingly, we found that concomitant postnatal deletion of Cox-1 and -2 over 10 months failed to cause intestinal injury in mice unless they were treated with naproxen or its structural analog, phenylpropionic acid, which is not a COX inhibitor. Cox double knockout mice exhibit a distinct gut microbiome composition and cohousing them with controls rescues their dysbiosis and delays the onset of NSAID-induced GI bleeding. In both the UK Biobank and All of Us human cohorts, coadministration of antibiotics with NSAIDs is associated with an increased frequency of GI bleeding. These results show that prostaglandin suppression plays a trivial role in NSAID-induced enteropathy. However, Cox deletion causes dysbiosis of the gut microbiome that amplifies the enteropathic response to NSAIDs.