Abstract
Background
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (INDO) and ibuprofen (IBU) has been shown to be an effective therapy for the closure of patent ductus arteriosus (PDA). However, this treatment has been associated with an increased risk of developing enteropathies in neonates. Whether the use of IBU is safer than INDO for the immature intestine remains to be elucidated.
Methods
The direct impact of IBU on the human immature intestinal transcriptome was investigated using serum-free organ culture. Differentially expressed genes were analyzed with Ingenuity Pathway Analysis software and compared with those previously reported with INDO. Validation of differentially expressed genes was confirmed by qPCR.
Results
We identified several biological processes that were significantly modulated by IBU at similar levels to what had previously been observed with INDO, while the expression of genes involved in “antimicrobial response” and “mucus production” was significantly decreased exclusively by IBU in the immature intestine.
Conclusions
Our findings indicate that IBU has a harmful influence on the immature intestine. In addition to exerting many of the INDO observed deleterious effects, IBU alters pathways regulating microbial colonization and intestinal epithelial defense.
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Acknowledgements
This work was supported by grants from the Canadian Institutes of Health Research (MOP136991) and the Stars Foundation. J.F.B. was the recipient of the Canada Research Chair in Intestinal Physiopathology.
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Ferretti, E., Tremblay, E., Thibault, MP. et al. Impaired antimicrobial response and mucosal protection induced by ibuprofen in the immature human intestine. Pediatr Res 84, 813–820 (2018). https://doi.org/10.1038/s41390-018-0201-y
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DOI: https://doi.org/10.1038/s41390-018-0201-y
