Altered intestinal and 5α-reductase gene levels in patients with hepatocellular carcinoma and elevated in atezolizumab/bevacizumab non-responders.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Monitoring of HCC and predicting its immunotherapy responses are challenging. This study explored the potential of the gut microbiome for HCC monitoring and predicting HCC immunotherapy responses. DNA samples were collected from the faeces of 22 patients with HCC treated with atezolizumab/bevacizumab (Atz/Bev) and 85 healthy controls. The gut microbiome was analysed using 16S rRNA next-generation sequencing and quantitative PCR (qPCR). The microbiomes of patients with HCC demonstrated significant enrichment of , particularly , and , notably . Comparative analysis between Atz/Bev responders (R) and non-responders (NR) revealed a higher abundance of in the NR group and in the R group. Using qPCR analysis, we observed elevated levels of and reduced levels of 5α-reductase genes, essential for the synthesis of isoallolithocholic acid, in HCC patients compared to controls. Additionally, the analysis confirmed a significantly lower abundance of in the Atz/Bev R group relative to the NR group. The gut microbiome analysis and specific gene quantification via qPCR could provide a rapid, less invasive, and cost-effective approach for assessing the increased risk of HCC, monitoring patient status, and predicting immunotherapy responses.