Correlation between the use of dried Toad skin-radix clematidis and the development of intestinal dysbiosis and colorectal cancer.

Objective: To examine the impact of different intestinal microbiota conditions on the absorption of couplet medicines (dried toad skin and radix clematidis) into the bloodstream, and to evaluate the therapeutic effects of drug-containing plasma, produced under different intestinal microbiota conditions, on colorectal cancer HT-29 cells.

Methods: In Experiment I, after the pseudo-sterile rat model was established, intragastric administration was performed. Explore the influence of different states of intestinal bacteria on rat organ coefficients, intestine bacteria, plasma metabolites, and so on. In Experiment II, the HT-29 cells of colon cancer were given to each group of drug-containing plasma for intervention to explore the intervention effect of HT-29-cell plasma produced under the influence of different states of intestinal bacteria.

Results: Pseudo-sterile conditions can affect the body weight, organ coefficients, and immune cell ratios of rats, leading to dysbiosis in various segments of their intestinal microbiota. After administering traditional Chinese medicine under pseudo-sterile conditions, the immune cell ratios in rats returned to normal, and the dysbiosis in the intestinal microbiota improved. There were 271 differential metabolites in the plasma between the groups. Cellular experiments indicate that plasma containing drugs obtained under normal gut microbiota conditions can significantly inhibit the proliferation and migration of HT-29 cells (p < 0.01), while the inhibitory effect of plasma containing drugs obtained under dysbiotic gut microbiota conditions is reduced (p < 0.05).

Conclusion: There is a bidirectional regulatory effect between the gut microbiota and the core medicinal pair. On one hand, dysbiosis weakens the efficacy of the medication. Dysbiosis can affect the blood components of the core medicinal pair. Compared to the drug-containing plasma produced under normal gut microbiota conditions, the drug-containing plasma produced under dysbiosis conditions has a reduced inhibitory effect on the proliferation of HT-29 cells. On the other hand, the drug repairs certain functions of the microbiota. After the drug enters the intestine, it exerts a positive regulatory effect on the dysbiosis of the intestinal microbiota in rats, partially improving the dysbiosis caused by antibiotics, restoring the balance of CD3+, CD4+, and CD8 + ratios in rats, and partially restoring the anticancer activity of drug-containing plasma.

Clinical trial number: not applicable.