Levels of Bile Acid Metabolism Are Associated With Alterations of Gut Microbes in Hepatocellular Carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is viewed as a metabolism associated disease, and bile acid metabolism is reported to occupy a significant role in the progression of HCC. However, little is known about the association between gut microbes and bile acid metabolism in HCC. Our study was designed to clarify the role of bile acid metabolism and microbiome in the progression of HCC. We investigated the relationship between bile acid metabolism and prognosis and immune cells by mining GSE14520. We studied the microbial profiles and metabolic alterations between the low bile acid group and high bile acid group using 16S rRNA sequencing and metabolomics. HCC patients in the high bile acid metabolism group showed better survival outcome compared with those in the low bile acid metabolism. Immune analysis displayed the close correlation between low bile acid metabolism and infiltration of CD4 + T cells, and the close relationship between high bile acid metabolism and infiltration of CD8 + T cells, macrophage cells in HCC. 16S rRNA sequencing results demonstrated that Blautia, Ruminococcus_gnavus_group, Erysipelotrichaceae_UCG‐003 were mostly enriched in the low bile acid group. Metabolomics of the 109 fecal samples showed that the most enriched metabolites in the low total bile acid group were dihydrocytochalasin B, cucurbic acid and 27‐Norcholestanehexol. Finally, KEGG enrichment analysis identified secondary bile acid biosynthesis and endocrine resistance as the most significant metabolic pathways. High bile acid metabolism was associated with more infiltration of CD8 + T cells, macrophage cells, and better prognosis in HCC. Levels of bile acid were significantly associated with altered gut microbes and metabolites in HCC. Further research related to gut microbes and bile acid metabolism may provide a novel insight into the pathogenesis and therapeutic strategy of HCC.