Crotonis Fructus-induced gut microbiota and serum metabolic disorders in rats

Crotonis Fructus (CF), a poisonous traditional laxative, has been used to treat constipation, edema, ascites, and inflammation for more than 2000 years. However, CF possesses toxicity and its toxic mechanism is still unclear. Thus, this research explored the deleterious impacts and underlying mechanisms of CF by evaluating alterations in gut microbiota composition and metabolites. High-throughput sequencing was employed on the 16S rDNA gene to explore the intestinal flora. The untargeted metabolomics method was utilized for evaluating serum metabolomics analysis. The results showed that CF could induce obvious hepatic and gastrointestinal damage by histopathologic morphology of the liver, stomach, duodenum, and colon. According to 16S rDNA sequencing, CF can cause gut microbiota disturbance in rats, and the abundance of opportunistic pathogens such as Clostridia_UCG_014_unclassified increased significantly, while the levels of beneficial bacterial Lactobacillus remarkably declined after CF treatment. Additionally, metabolomics analysis demonstrated that CF may induce toxicity by disrupting the glycerophospholipid metabolism pathway and metabolites such as phosphatidylcholine and phosphatidylethanolamine. Moreover, a correlation study revealed the link between intestinal flora, serum metabolites, and toxicity-related biochemical markers. The results provide a new idea for the research and clinical application of toxic traditional medicine. KEY POINTS: • Crotonis Fructus could affect the gut flora and serum metabolic disruption in SD rats. • Crotonis Fructus could promote the proliferation of harmful bacteria and inhibit beneficial bacteria. • Glycerophospholipid metabolism was disturbed by Crotonis Fructus.