Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites
Zhang X, Coker OO, Chu ES, Fu K, Lau HCH, Wang YX, Chan AWH, Wei H, Yang X, Sung JJY, Yu J
Gut · 732 citas
Etiquetas de revisión
Sin ajuste declarado por estilo de vidaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio de casos y controles (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Natural Science Foundation of Guangdong Province
- Universidad u hospital
- Chinese University of Hong Kong
- Gobierno
- Guangdong Natural Science Foundation
- Gobierno
- RGC Collaborative Research Fund
- Universidad u hospital
- Vice-Chancellor's Discretionary Fund CUHK
- Gobierno
- RGC Theme-based Research Scheme Hong Kong
- Universidad u hospital
- CUHK direct grant for research
- Subvenciones
- Natural Science Foundation of Guangdong Province (2018B030312009)
Según 7 financiadores declarados.
Publicación
- Publicado
- 2020-07-21 · Gut · vol. 70 · número 4 · págs. 761–774
- Editorial
- BMJ
- Citado
- 838 citas · más que el 100% de estudios similares · 24.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 44 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC
- Áreas de investigación
- Gut microbiota and health · Liver Disease Diagnosis and Treatment · Metabolomics and Mass Spectrometry Studies
- Palabras clave
- Steatohepatitis, Gut flora, Dysbiosis, Fatty liver, Internal medicine, Cholesterol, Steatosis, Dyslipidemia, Endocrinology, Atorvastatin, Taurocholic acid, Biology, Bile acid, Medicine, Immunology, Diabetes mellitus, Disease
- MeSH
- animals, mice, inbred c57bl, mice, carcinoma, hepatocellular, liver neoplasms, disease progression, cholesterol, dietary, case-control studies, male, non-alcoholic fatty liver disease, gastrointestinal microbiome, fecal microbiota transplantation, atorvastatin
11 autores
- Xiang Zhang🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Olabisi Oluwabukola Coker🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Eagle SH Chu🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Kaili Fu🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Harry Cheuk-Hay Lau🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Yi-Xiang Wang🇭🇰Chinese University of Hong Kong
- Anthony W.H. Chan🇭🇰Chinese University of Hong Kong
- Hong Wei🇨🇳Army Medical University; Sun Yat-sen University; The First Affiliated Hospital, Sun Yat-sen University
- Xiaoyong Yang🇺🇸Yale University
- Joseph J.�Y. Sung🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Jun Yu🇭🇰🇨🇳 · autor de correspondenciaChinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
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.
Design
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.
Results
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, Anaerotruncus and Desulfovibrionaceae increased sequentially; while Bifidobacterium and Bacteroides were depleted in HFHC-fed mice, which was corroborated in human hypercholesteremia patients. Dietary cholesterol induced gut bacterial metabolites alteration including increased taurocholic acid and decreased 3-indolepropionic acid. Germ-free mice gavaged with stools from mice fed HFHC manifested hepatic lipid accumulation, inflammation and cell proliferation. Moreover, atorvastatin restored cholesterol-induced gut microbiota dysbiosis and completely prevented NAFLD-HCC development.
Conclusions
Dietary cholesterol drives NAFLD-HCC formation by inducing alteration of gut microbiota and metabolites in mice. Cholesterol inhibitory therapy and gut microbiota manipulation may be effective strategies for NAFLD-HCC prevention.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC).
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