Effect of Transarterial Chemotherapy on the Structure and Function of Gut Microbiota in New Zealand White Rabbits

TL;DR

This study shows that hepatic arterial chemotherapy in rabbits disrupts gut microbiota balance, leading to harmful bacterial growth and inflammation, which could explain gastrointestinal side effects in cancer patients.

Contribution

The study provides new insights into how transarterial chemotherapy alters gut microbiota composition and function, linking these changes to inflammatory pathways and gastrointestinal toxicity.

Findings

Hepatic arterial chemotherapy with epirubicin reduces Firmicutes and increases Proteobacteria in rabbit gut microbiota.

Chemotherapy disrupts intestinal barrier function and activates inflammatory pathways like LPS-TLR-4-pSTAT3.

Changes in gut microbiota after chemotherapy peak on day 4 and show partial recovery by day 7.

Abstract

Gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased, and beneficial bacteria decreased, while harmful bacteria increased. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day.

The gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. Therefore, we conducted animal experiments to investigate these changes. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased. The relative abundance of beneficial bacteria, such as Muribaculaceae, Enterococcus, Ruminococcus, and Clostridia, decreased in the experimental group compared with those in the control group. However, the relative abundance of harmful bacteria, such as Bacteroides and Escherichia (Shigella), was higher in the experimental group than in the control group. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day. The changes in the host’s GM before and after arterial chemotherapy are evident. Hepatic arterial chemotherapy induces dysbiosis of the intestinal microbiota, disrupts intestinal barrier function, damages the integrity of the intestinal mucosa, increases intestinal permeability, facilitates excessive passage of harmful substances through the gut–liver axis communication between the liver and intestine, and triggers activation of inflammatory pathways such as LPS-TLR-4-pSTAT3, ultimately leading to an inflammatory response. This study provides a theoretical basis for combining TACE with targeted GM intervention to treat HCC and reduce adverse gastrointestinal reactions.

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