Guild-Level Gut Microbial Alterations Associate with Non-hepatitis Virus related Hepatocellular Carcinoma

The gut microbiota of hepatocellular carcinoma (HCC) is different from that of cohort without HCC. However, the relationship between non-hepatitis virus related HCC and gut microbial alterations remains elusive. In this work, we studied the gut microbial data in Sequence Read Archive (SRA) database from 58 healthy controls (HC), 31 patients with nonalcoholic fatty liver disease (NAFLD), 206 patients with hepatitis B viruses, 35 patients with HBV related HCC (B-HCC), and 22 patients with non-HBV or non-HCV related HCC (NBNC-HCC). Depend on guild-based analysis, 27 gut bacterial co-abundance groups (CAGs) were established. By studying these CAGs, we found the gut microbial overall structure and composition differed among patients with NBNC-HCC, B-HCC, other liver diseases, and healthy cohort, such as members from Lachnospiraceae, Veillonellaceae, and Prevotella. The network calculated by these CAGs in patients with HCC showed less interactions than that in healthy cohort. The specific CAGs showed correlated to the development of HCC. In addition, gut bacterial dysbiosis index, which was calculated by significantly altered CAGs in patients with NBNC-HCC compared with healthy cohort, showed potential diagnostic power of NBNC-HCC. Therefore, this study shows a new way toward understanding the role of the gut microbiome in patients with non-hepatitis virus related HCC. IMPORTANCEGut microbiome may play an important role in the pathogenesis and development of hepatocellular carcinoma. However, the relationship between non-hepatitis virus related hepatocellular carcinoma and gut microbiome should be further understood. In the current work, we found the alterations of gut microbial structure, composition, and network robustness in these patients by guild-based data analysis. Specific gut bacteria in these patients were related to clinical parameters, such as blood biochemical indexes. More importantly, gut bacterial bio-markers, which can discriminate these patients and cohort without this disease, were showed in this study. Thus, our study suggests that these guild-level gut bacteria may contribute to the development of non-hepatitis virus related hepatocellular carcinoma. This provides a new direction for future studies, which aims to show the importance of the gut microbiome in hepatocellular carcinoma.