1. Microbiome, fibrosis and tumor networks in a non-alcoholic steatohepatitis model of a choline-deficient high-fat diet using diethylnitrosamine.
- Author
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Yamamoto K, Honda T, Yokoyama S, Ma L, Kato A, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Kawashima H, Ishigami M, Tsuji NM, and Fujishiro M
- Subjects
- Animals, Carcinogenesis metabolism, Carcinoma, Hepatocellular microbiology, Cyclin-Dependent Kinase Inhibitor p21, Humans, Liver Neoplasms microbiology, Mice, Mice, Inbred C57BL, Microbiota, Non-alcoholic Fatty Liver Disease complications, Random Allocation, Alkylating Agents metabolism, Carcinoma, Hepatocellular pathology, Choline Deficiency metabolism, Diethylnitrosamine metabolism, Liver Neoplasms pathology
- Abstract
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), choline-deficient 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., Competing Interests: Declaration of Competing Interest Dr. Tsuji reports grants from the Japan Society for the Promotion of Science (JSPS), during the conduct of the study., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2021
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