Microbiome, fibrosis and tumor networks in a non-alcoholic steatohepatitis model of a choline-deficient high-fat diet using diethylnitrosamine

被引：9

作者：

Yamamoto, Kenta ^{[1
]}

Honda, Takashi ^{[1
]}

Yokoyama, Shinya ^{[1
]}

Ma, Lingyun ^{[1
]}

Kato, Asuka ^{[1
]}

Ito, Takanori ^{[1
]}

Ishizu, Yoji ^{[1
]}

Kuzuya, Teiji ^{[1
]}

Nakamura, Masanao ^{[1
]}

Kawashima, Hiroki ^{[1
]}

Ishigami, Masatoshi ^{[1
]}

Tsuji, Noriko M. ^{[2
]}

Fujishiro, Mitsuhiro ^{[1
]}

机构：

[1] Nagoya Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Showa Ku, 65 Tsuruma Cho, Nagoya, Aichi 4668550, Japan

[2] Natl Inst Adv Ind Sci & Technol, Res Inst, Tsukuba, Ibaraki 3058566, Japan

来源：

DIGESTIVE AND LIVER DISEASE | 2021年 / 53卷 / 11期

基金：

日本学术振兴会;

关键词：

Cirrhosis; Hepatocellular carcinoma; Liver; Feces; Microbiome; Fibrosis; LIVER; CANCER; NASH;

D O I：

10.1016/j.dld.2021.02.013

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & aims: Hepatocellular carcinoma in nonalcoholic steatohepatitis is caused by the complex factors of inflammation, fibrosis and microbiomes. We used network analysis to examine the interrelationships of these factors. Methods: C57Bl/6 mice were categorized into groups: choline-sufficient high-fat (CSHF, n = 8), cholinedeficient high-fat (CDHF, n = 9), and CDHF + diethylnitrosamine (DEN, n = 8). All mice were fed CSHF or CDHF for 20 weeks starting at week 8, and mice in the CDHF + DEN group received one injection of DEN at 3 weeks of age. Bacterial gene was isolated from feces and analyzed using Miseq. Results: The CSHF group had less fibrosis than the other groups. Tumors were found in 22.2% and 87.5% of the CDHF group and CDHF + DEN groups, respectively. Gene expression in the liver of Cdkn1a (p21: tumor-suppressor) and c-jun was highest in the CDHF group. Bacteroides, Roseburia, Odoribacter, and Clostridium correlated with fibrosis. Streptococcus and Dorea correlated with inflammation and tumors. Akkermansia and Bilophila were inversely correlated with fibrosis and Bifidobacterium was inversely correlated with tumors. Conclusions: DEN suppressed the overexpression of p21 caused by CDHF. Some bacteria formed a relationship networking associated with their progression and inhibition for tumors and fibrosis. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

引用

页码：1443 / 1450

页数：8

共 24 条

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