Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites.

Gut
Xiang ZhangJun Yu

Abstract

Non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is an increasing healthcare burden worldwide. We examined the role of dietary cholesterol in driving NAFLD-HCC through modulating gut microbiota and its metabolites. High-fat/high-cholesterol (HFHC), high-fat/low-cholesterol or normal chow diet was fed to C57BL/6 male littermates for 14 months. Cholesterol-lowering drug atorvastatin was administered to HFHC-fed mice. Germ-free mice were transplanted with stools from mice fed different diets to determine the direct role of cholesterol modulated-microbiota in NAFLD-HCC. Gut microbiota was analysed by 16S rRNA sequencing and serum metabolites by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Faecal microbial compositions were examined in 59 hypercholesterolemia patients and 39 healthy controls. High dietary cholesterol led to the sequential progression of steatosis, steatohepatitis, fibrosis and eventually HCC in mice, concomitant with insulin resistance. Cholesterol-induced NAFLD-HCC formation was associated with gut microbiota dysbiosis. The microbiota composition clustered distinctly along stages of steatosis, steatohepatitis and HCC. Mucispirillum, Desulfovibrio, Anaerotr...Continue Reading

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Citations

Dec 18, 2020·Current Opinion in Lipidology·Manon BalversMax Nieuwdorp
Jan 27, 2021·Metabolism: Clinical and Experimental·Ge YangXin Jiang
Apr 14, 2021·Nucleic Acids Research·Muhammad ArifAdil Mardinoglu
Apr 22, 2021·Journal of Gastroenterology and Hepatology·Tao ZengZhangran Chen
Apr 27, 2021·Pharmacology & Therapeutics·Xiao-Yuan MaoWei-Lin Jin
May 6, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xueliang WangGuangli Yu
May 30, 2021·European Journal of Clinical Investigation·Agnieszka Karkucinska-WieckowskaMariusz R Wieckowski
Aug 18, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Linlin ChenHoukai Li
Aug 27, 2021·Metabolites·Kiera MurphyCatherine Stanton
Apr 25, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xia YangZhi-Gang She
Oct 20, 2021·Journal of Gastroenterology and Hepatology·Yasi Pan, Xiang Zhang
Nov 7, 2021·Nature Reviews. Immunology·Thierry Huby, Emmanuel L Gautier

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