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

<b>Introduction.</b> Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide.<b>Gap statement.</b> Monitoring of HCC and predicting its immunotherapy responses are challenging.<b>Aim.</b> This study explored the potential of the gut microbiome for HCC monitoring and predicting HCC immunotherapy responses.<b>Methods.</b> 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).<b>Results.</b> The microbiomes of patients with HCC demonstrated significant enrichment of <i>Lactobacillus</i>, particularly <i>Lactobacillus fermentum</i>, and <i>Streptococcus</i>, notably <i>Streptococcus anginosus</i>. Comparative analysis between Atz/Bev responders (R) and non-responders (NR) revealed a higher abundance of <i>Bacteroides stercoris</i> in the NR group and <i>Bacteroides coprocola</i> in the R group. Using qPCR analysis, we observed elevated levels of <i>S. anginosus</i> 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 <i>B. stercoris</i> in the Atz/Bev R group relative to the NR group.<b>Conclusions.</b> 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.