Intestinal Candida albicans Promotes Hepatocarcinogenesis by Up-Regulating NLRP6

Abstract

Hepatocellular carcinoma (HCC), a primary liver cancer, is closely associated with the gut microbiota. However, the role of gut fungi in the development of HCC remains unclear. The aim of this study was to explore the influence of intestinalCandida albicanson HCC. Here, We found that patients with HCC showed significantly decreased diversity of the gut mycobiome and increased abundance ofC. albicans, compared to the patients with liver cirrhosis. The gavage ofC. albicansin the WT models increased the tumor size and weight and influenced the plasma metabolome, which was indicated by alterations in 117 metabolites, such as L-carnitine and L-acetylcarnitine, and several KEGG enriched pathways, such as phenylalanine metabolism and citrate cycle. Moreover, the expression of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in the intestinal tissues and primary intestinal epithelial cells of the WT mice interacted withC. albicansincreased. Notably, the colonization ofC. albicanshad no effect on tumor growth inNlrp6–/–mice. In conclusion, the abnormal colonization ofC. albicansreprogrammed HCC metabolism and contributed to the progression of HCC dependent on NLRP6, which provided new targets for the treatment of HCC.