Microbiome, fibrosis and tumor networks in a non-alcoholic steatohepatitis model of a choline-deficient high-fat diet using diethylnitrosamine.
Alkylating Agents
/ metabolism
Animals
Carcinogenesis
/ metabolism
Carcinoma, Hepatocellular
/ microbiology
Choline Deficiency
/ metabolism
Cyclin-Dependent Kinase Inhibitor p21
Diethylnitrosamine
/ metabolism
Humans
Liver Neoplasms
/ microbiology
Mice
Mice, Inbred C57BL
Microbiota
Non-alcoholic Fatty Liver Disease
/ complications
Random Allocation
Cirrhosis
Feces
Fibrosis
Hepatocellular carcinoma
Liver
Microbiome
Journal
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
29
08
2020
revised:
10
02
2021
accepted:
11
02
2021
pubmed:
18
3
2021
medline:
8
2
2022
entrez:
17
3
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
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
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
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
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.
Identifiants
pubmed: 33726979
pii: S1590-8658(21)00081-5
doi: 10.1016/j.dld.2021.02.013
pii:
doi:
Substances chimiques
Alkylating Agents
0
Cdkn1a protein, mouse
0
Cyclin-Dependent Kinase Inhibitor p21
0
Diethylnitrosamine
3IQ78TTX1A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1443-1450Informations de copyright
Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Dr. Tsuji reports grants from the Japan Society for the Promotion of Science (JSPS), during the conduct of the study.