Chlorogenic acid alleviates the intestinal barrier dysfunction and intestinal flora disorder induced by cisplatin

Abstract This article conducted research and analysis on the relationship between cisplatin induced intestinal barrier disruption, gut microbiota imbalance, and the protect effect of chlorogenic acid (CGA) on gastro intestine. This article selected C57BL/6J mice as the research object, with an age of 4 weeks and a total of 28 mice. The mice were divided into 4 groups, including the control group (CN), a cisplatin (Cis) group, a CGA treatment group receiving intraperitoneal injections alongside cisplatin (Cis + CGA1), and the last group pre-treated with CGA before cisplatin administration (Cis + CGA2). This study used RT qPCR to determine IL-6, IL-1β and TNF-ɑ mRNA, while serum levels of these cytokines and fecal LPS were determined through ELISA. Western blot was used to analyze the expression of Occludin and ZO-1 proteins in colon tissue, and H&E staining to study the histopathological conditions of the colon tissue. Moreover, this article also utilized high-throughput sequencing to analyze the gut microbiota of feces. The results indicated that CGA administration reduced IL-6, IL-1β and TNF-α level in both colon tissue and serum compared to the Cis group. CGA pretreatment notably enhanced the expression of Occludin and ZO-1 proteins in colon tissues, improved intestinal barrier integrity. Histopathological analysis confirmed the reduction in intestinal inflammation injury with CGA treatment. Moreover, 16S rDNA sequencing showed that while Bacteroidetes and Firmicutes predominated in the control group, the Cis group saw a rise in Proteobacteria, with a notable shift in the gut microbiota's composition and a decrease in α diversity. CGA treatment was able to mitigate these changes induced by cisplatin. All results suggest CGA effectively mitigates the inflammatory response and destruction of the mucosal barrier in the intestines caused by cisplatin, offering a protective effect against the disturbances of intestinal flora.