# Exploratory Analysis of Gut Microbiome and Metabolic Profile Changes Following Lenvatinib and Anti-PD-1 Combination Therapy in Liver Cancer

## TL;DR

This study explores how gut bacteria and metabolism change in mice with liver cancer before and after treatment with lenvatinib and anti-PD-1 therapy.

## Contribution

The study identifies specific gut microbiota and metabolite changes associated with lenvatinib and anti-PD-1 combination therapy in liver cancer.

## Key findings

- Combination therapy reduced certain gut bacteria like Lactobacillus and Clostridium while increasing Prevotella_7.
- Metabolite levels such as pyridoxic acid and deoxycholic acid increased, while myristic acid and uric acid decreased.
- The treatment partially reversed gut microbiome and metabolic changes caused by liver cancer in mice.

## Abstract

Background/Objectives: Lenvatinib combined with anti-PD-1 therapy has shown promise in the treatment of hepatocellular carcinoma (HCC). The study evaluates changes in gut microbiota (GM) and metabolites during HCC treatment with lenvatinib combined with anti-PD-1. Methods: An HCC mouse model was established via diethylnitrosamine (DEN) injection, and the mice were then treated with lenvatinib, anti-PD-1, or their combination. GM composition and structural changes were assessed by 16S rDNA sequencing, and metabolite abundance by liquid chromatography–mass spectrometry (LC–MS). Results: Significant alterations in GM and metabolites were observed in the HCC group compared to the control group, and compared with the HCC group, both monotherapy and combination therapy resulted in varying degrees of GM and metabolites rebalancing. Specifically, compared to the HCC group, lenvatinib combined with anti-PD-1 therapy decreased the abundance of GM, including p_Patescibacteria, g_Lactobacillus, g_Clostridium_sensu_stricto_1, g_Eubacterium_siraeum_group, and g_Desulfovibrio, while the abundance of g_Prevotella_7 increased. Metabolite changes included increased 4-pyridoxic acid, deoxycholic acid, and taurochenodesoxycholic acid, and decreased myristic acid, oleic acid, riboflavin, and uric acid. Conclusions: HCC induces substantial alterations in the GM and metabolic profile of mice. Lenvatinib combined with anti-PD-1 treatment partially modulates these dysregulations. The relevant GM and metabolites may be associated with the efficacy of combined therapy and could serve as potential markers for further investigation.