The Interaction Between Intratumoral Bacteria and Metabolic Distortion in Hepatocellular Carcinoma

Background Intratumoral bacteria might play essential roles in tumorigenesis in different cancer types. However, its features and potential roles in hepatocellular carcinoma (HCC) are largely unknown. Methods In this study, we assessed bacterial RNA by 16S rRNA fluorescence in situ hybridization and detected bacterial lipopolysaccharide (LPS) via immunohistochemistry. Hepa1-6 cells were used to establish orthotopic HCC models in mice. 2bRAD sequencing for microbiome was performed to determine the intratumoral bacterial characteristics, and liquid chromatography-mass spectrometry was conducted to explore the metabolic profile. The potential association between different intratumoral microbiota and metabolites were evaluated. Results We detected bacterial 16S rRNA and LPS in HCC tissues from the patients with HCC. In HCC mouse model, we found that the intratumor bacteria in HCC tissues were significantly different to adjacent nontumor tissues. Furthermore, we observed different metabolites in HCC tissues and adjacent nontumor tissues, such as N-acetyl-D-glucosamine and a-lactose. Our results showed that several bacteria were significantly associated with metabolites, such as Pseudomonas koreensis , which was positively correlated with N-acetyl-D-glucosamine and negatively correlated with citrulline. Conclusions This study confirmed the close association between different bacteria and metabolites, which might provide novel opportunities for developing new biomarkers and therapeutic targets for HCC.