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Updated: Mar 21, 2026
Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Identification and Evaluation of Novel MicroRNA Biomarkers in Plasma and Feces Associated with Drug-induced
Dalia Y Kalabat1, Allison Vitsky1, Wesley Scott1
11 Drug Safety R&D, Pfizer Global R&D, San Diego, California, USA.
Abstract:
Gastrointestinal toxicity is dose limiting with many therapeutic and anticancer agents. Real-time, noninvasive detection of markers of toxicity in biofluids is advantageous. Ongoing research has revealed microRNAs as potential diagnostic and predictive biomarkers for the detection of select organ toxicities. To study the potential utility of microRNA biomarkers of intestinal injury in a preclinical toxicology species, we evaluated 3 rodent models of drug-induced intestinal toxicity, each with a distinct mechanism of toxicity. MiR-215 and miR-194 were identified as putative intestinal toxicity biomarkers. Both were evaluated in plasma and feces and compared to plasma citrulline, an established intestinal injury biomarker. Following intestinal toxicant dosing, microRNA changes in feces and plasma were detected noninvasively and correlated with histologic evidence of intestinal injury. Fecal miR-215 and miR-194 levels increased, and plasma miR-215 decreased in a dose- and time-dependent manner. Dose-dependent decreases in plasma miR-215 levels also preceded and correlated positively with plasma citrulline modulation, suggesting miR-215 is a more sensitive biomarker. Moreover, during the drug-free recovery phase, plasma miR-215 returned to predose levels, supporting a corresponding recovery of histologic lesions. Despite limitations, this study provides preliminary evidence that select microRNAs have the potential to act as noninvasive, sensitive, and quantitative biomarkers of intestinal injury.
Insights
New research identifies microRNAs (miRNAs) as promising noninvasive biomarkers for detecting drug-induced intestinal toxicity. Fecal miR-215 and miR-194 increased, while plasma miR-215 decreased, correlating with injury and recovery.
Area of Science:
- Toxicology
- Molecular Biology
- Biomarker Discovery
Background:
- Gastrointestinal toxicity is a significant dose-limiting factor for many therapeutic and anticancer agents.
- Noninvasive, real-time detection of toxicity markers in biofluids is highly desirable for patient safety.
- MicroRNAs (miRNAs) are emerging as potential diagnostic and predictive biomarkers for organ toxicities.
Purpose of the Study:
- To evaluate the utility of miRNA biomarkers for detecting drug-induced intestinal injury.
- To identify specific miRNAs that can serve as noninvasive biomarkers of intestinal toxicity in preclinical models.
- To compare miRNA biomarker candidates with established markers like plasma citrulline.
Main Methods:
- Utilized three rodent models of drug-induced intestinal toxicity with distinct mechanisms.
- Quantified levels of miR-215 and miR-194 in plasma and feces following toxicant administration.
- Correlated miRNA levels with histological evidence of intestinal injury and plasma citrulline levels.
Main Results:
- Fecal miR-215 and miR-194 levels increased, while plasma miR-215 decreased in a dose- and time-dependent manner.
- Changes in fecal and plasma miRNAs were detected noninvasively and correlated with histological intestinal injury.
- Decreases in plasma miR-215 preceded and positively correlated with plasma citrulline modulation, indicating higher sensitivity.
Conclusions:
- Preliminary evidence suggests miR-215 and miR-194 are potential noninvasive biomarkers of intestinal injury.
- Plasma miR-215 demonstrated sensitivity and indicated recovery of intestinal lesions.
- Further research is warranted to validate these miRNAs as reliable biomarkers in clinical settings.
