Intestinal Candida albicans Promotes Hepatocarcinogenesis by Up-Regulating NLRP6

Autor: Zherui Liu, Yinyin Li, Chen Li, Guanglin Lei, Lin Zhou, Xiangling Chen, Xiaodong Jia, Yinying Lu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Microbiology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-302X
DOI: 10.3389/fmicb.2022.812771
Popis: 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.
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