Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease  

作　　者：Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li 

机构地区：[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,National Medical Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [2]Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China

出　　处：《Science China(Life Sciences)》2024年第6期1183-1198,共16页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(81790631);the National Key Research and Development Program of China(2022YFC3602000);the Shandong Provincial Laboratory Project(SYS202202);Research Project of Jinan Micro-ecological Biomedicine Shandong Laboratory(JNL-2022009B,JNL-2022047D)。

摘　　要：Liver disease,a major health concern worldwide,is a serious and progressive disorder.Herein,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut mycobiome.As liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse models.The metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC group.The abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in HCC.Based on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were depleted.The increased abundance of C.albicans and depletion of S.cerevisiae may be hallmarks of the progression of liver cirrhosis to early HCC.Moreover,the administration of C.albicans and S.cerevisiae in the LC-HCC progression could accelerate or retard the progression of HCC.Therefore,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关 键 词：gut mycobiome liver disease longitudinal studies HEPATOCARCINOGENESIS fungal biomarker 

分 类 号：R575[医药卫生—消化系统]