Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used classes of medications in the world, yet they induce an enteropathy that is associated with high morbidity and mortality. A major limitation to better understanding the pathophysiology and diagnosis of this enteropathy is the difficulty of obtaining information about the primary site of injury, namely the distal small intestine. We investigated the utility of using mRNA from exfoliated cells in stool as a means to surveil the distal small intestine in a murine model of NSAID enteropathy. Specifically, we performed RNA-Seq on exfoliated cells found in feces and compared these data to RNA-Seq from both the small intestinal mucosa and colonic mucosa of healthy control mice or those exhibiting NSAID-induced enteropathy. Global gene expression analysis, data intersection, pathway analysis, and computational approaches including linear discriminant analysis (LDA) and sparse canonical correlation analysis (CCA) were used to assess the inter-relatedness of tissue (invasive) and stool (noninvasive) datasets. These analyses revealed that the exfoliated cell transcriptome closely mirrored the transcriptome of the small intestinal mucosa. Thus, the exfoliome may serve as a non-invasive means of detecting and monitoring NSAID enteropathy (and possibly other gastrointestinal mucosal inflammatory diseases).
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently consumed pharmaceuticals worldwide because of their anti-inflammatory, anti-neoplastic, and analgesic effects
Our specific aims were: 1) to determine whether the transcriptome of exfoliated cells reflected gene expression of the small intestinal mucosa; 2) to demonstrate that the transcriptome of exfoliated cells can be used to differentiate healthy and diseased phenotypes; and, 3) to generate hypotheses regarding key biological pathways and processes involved in the pathogenesis of NSAID enteropathy
After extracting RNA from tissues and exfoliated cells we examined RNA quality owing to the potential for degradation of mRNA from exfoliated SI cells in stool as it passes through the GI tract
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently consumed pharmaceuticals worldwide because of their anti-inflammatory, anti-neoplastic, and analgesic effects Their use can result in an enteropathy that has an alarmingly high rate of morbidity and mortality. We applied computational approaches, e.g., linear discriminant analysis (LDA) and sparse canonical correlation analysis (CCA), to analyze the inter-relatedness of these data The goals of these studies were to provide proof-of-principle that the exfoliated cell transcriptome (i.e., the exfoliome) could be used to gain information about NSAID-induced small intestinal injury. Our specific aims were: 1) to determine whether the transcriptome of exfoliated cells reflected gene expression of the small intestinal mucosa; 2) to demonstrate that the transcriptome of exfoliated cells can be used to differentiate healthy and diseased phenotypes; and, 3) to generate hypotheses regarding key biological pathways and processes involved in the pathogenesis of NSAID enteropathy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
