Acute oral colchicine caused gastric mucosal injury and disturbance of associated microbiota in mice.

Abstract

Colchicine (COL), an ancient and well-known drug, has been used in clinical practice for centuries. On the other hand, COL has also attracted extensive concerns for its potent toxic effects, especially gastrointestinal adverse reactions (nausea, vomiting, and diarrhea) before clinical symptoms relief. In this study, we used a rodent model to study the effects of COL on gastric mucosa and associated microbiota. The mice were exposed to various concentrations of COL (0.1, 0.5, and 2.5 mg kg-1 body weight per day) for 7 days, and the results showed that COL treatment caused severe gastric mucosal damage, accompanied by a significant decrease in gastric mucosal proinflammatory cytokines (IL-1β, IL-6, and TNF-α). The 16S rRNA gene sequencing revealed that COL significantly perturbed the gastric microbiota composition and reduced the gastric microbiota diversity in mice. Also, we identified bacterial biomarkers associated with diarrhea, including phylum Firmicutes, class Bacilli, order Lactobacillales, family Lactobacillaceae, genu Lactobacillus, and genu Blautia, suggesting that COL-triggered adverse reactions are closely related to gastric microbial perturbations. Our findings open new paths for understanding the mechanism of COL-related adverse gastrointestinal reactions, broadening the scientific view on the interaction between drugs and host gastrointestinal microbiota.