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 intestinal Candida albicans on HCC. Here, We found that patients with HCC showed significantly decreased diversity of the gut mycobiome and increased abundance of C. albicans, compared to the patients with liver cirrhosis. The gavage of C. albicans in 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 with C. albicans increased. Notably, the colonization of C. albicans had no effect on tumor growth in Nlrp6–/– mice. In conclusion, the abnormal colonization of C. albicans reprogrammed HCC metabolism and contributed to the progression of HCC dependent on NLRP6, which provided new targets for the treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide (Yu and Schwabe, 2017)
Principal coordinate analysis results showed that the HCC and liver cirrhosis (LC) groups aggregated separately, suggesting that the gut fungal community had a different distribution in the HCC and LC groups (Figure 1C)
The fungal profiling was performed for each subject to identify the main taxon at the order, family and genus level (Figures 2A–C). These results reveal that the composition of gut fungi in patients with HCC is significantly altered compared to that in patients with LC
Summary
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide (Yu and Schwabe, 2017). The gut microbiota, known as the microflora, is considered the most important microecosystem in the human body, consisting of bacteria, archaea, viruses, and fungi (Eckburg et al, 2005; Li et al, 2019). Studies on gut microbiota and HCC emphasize bacteria while neglecting fungi because of their decreased abundance (Huffnagle and Noverr, 2013). Intestinal fungi affect the conditions of the gut and the functions of other extraintestinal organs, including the liver (Wu X. et al, 2021). Several liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, and cirrhosis have been closely associated with
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