Transcriptomic Profiling Identifies Novel Hepatic and Intestinal Genes Following Chronic Plus Binge Ethanol Feeding in Mice.
Animals
Central Nervous System Depressants
/ pharmacology
Cholic Acid
/ analysis
Correlation of Data
Down-Regulation
Ethanol
/ pharmacology
Gastrointestinal Hormones
/ genetics
Gastrointestinal Microbiome
/ drug effects
Gene Expression Profiling
/ methods
Intestines
/ drug effects
Liver
/ drug effects
Liver Diseases, Alcoholic
/ metabolism
Mice
Neuropeptides
/ genetics
Organic Cation Transport Proteins
/ genetics
Sequence Analysis, RNA
/ methods
16S rDNA sequencing
Bile acids
Gene expression
Metabolome
Microbiome
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
26
05
2020
accepted:
28
06
2020
pubmed:
17
7
2020
medline:
5
2
2021
entrez:
17
7
2020
Statut:
ppublish
Résumé
Alcohol-associated liver disease accounts for half of cirrhosis-related deaths worldwide. The spectrum of disease varies from simple steatosis to fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Understanding the disease on a molecular level helps us to develop therapeutic targets. We performed transcriptomic analysis in liver and ileum from chronic plus binge ethanol-fed mice, and we assessed the role of selected differentially expressed genes and their association with serum bile acids and gut microbiota. Wild-type mice were subjected to a chronic Lieber-DeCarli diet model for 8 weeks followed by one binge of ethanol. RNA-seq analysis was performed on liver and ileum samples. Associations between selected differentially regulated genes and serum bile acid profile or fecal bacterial profiling (16S rDNA sequencing) were investigated. We provide a comprehensive transcriptomic analysis to identify differentially expressed genes, KEGG pathways, and gene ontology functions in liver and ileum from chronic plus binge ethanol-fed mice. In liver, we identified solute carrier organic anion transporter family, member 1a1 (Slco1a1; encoding for organic anion transporting polypeptides (OATP) 1A1), as the most down-regulated mRNA, and it is negatively correlated with serum cholic acid level. Prokineticin 2 (Prok2) mRNA, a cytokine-like molecule associated with gastrointestinal tract inflammation, was significantly down-regulated in ethanol-fed mice. Prok2 mRNA expression was negatively correlated with abundance of Allobaculum (genus), Coprococcus (genus), Lachnospiraceae (family), Lactococcus (genus), and Cobriobacteriaceae (family), while it positively correlated with Bacteroides (genus). RNA-seq analysis revealed unique transcriptomic signatures in the liver and intestine following chronic plus binge ethanol feeding.
Sections du résumé
BACKGROUND
Alcohol-associated liver disease accounts for half of cirrhosis-related deaths worldwide. The spectrum of disease varies from simple steatosis to fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Understanding the disease on a molecular level helps us to develop therapeutic targets.
AIM
We performed transcriptomic analysis in liver and ileum from chronic plus binge ethanol-fed mice, and we assessed the role of selected differentially expressed genes and their association with serum bile acids and gut microbiota.
METHODS
Wild-type mice were subjected to a chronic Lieber-DeCarli diet model for 8 weeks followed by one binge of ethanol. RNA-seq analysis was performed on liver and ileum samples. Associations between selected differentially regulated genes and serum bile acid profile or fecal bacterial profiling (16S rDNA sequencing) were investigated.
RESULTS
We provide a comprehensive transcriptomic analysis to identify differentially expressed genes, KEGG pathways, and gene ontology functions in liver and ileum from chronic plus binge ethanol-fed mice. In liver, we identified solute carrier organic anion transporter family, member 1a1 (Slco1a1; encoding for organic anion transporting polypeptides (OATP) 1A1), as the most down-regulated mRNA, and it is negatively correlated with serum cholic acid level. Prokineticin 2 (Prok2) mRNA, a cytokine-like molecule associated with gastrointestinal tract inflammation, was significantly down-regulated in ethanol-fed mice. Prok2 mRNA expression was negatively correlated with abundance of Allobaculum (genus), Coprococcus (genus), Lachnospiraceae (family), Lactococcus (genus), and Cobriobacteriaceae (family), while it positively correlated with Bacteroides (genus).
CONCLUSIONS
RNA-seq analysis revealed unique transcriptomic signatures in the liver and intestine following chronic plus binge ethanol feeding.
Identifiants
pubmed: 32671585
doi: 10.1007/s10620-020-06461-6
pii: 10.1007/s10620-020-06461-6
pmc: PMC7669632
mid: NIHMS1612389
doi:
Substances chimiques
Central Nervous System Depressants
0
Gastrointestinal Hormones
0
Neuropeptides
0
Oatp1a1 protein, mouse
0
Organic Cation Transport Proteins
0
Prok2 protein, mouse
0
Ethanol
3K9958V90M
Cholic Acid
G1JO7801AE
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3592-3604Subventions
Organisme : BLRD VA
ID : I01 BX004594
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120515
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA024726
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA011999
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA026939
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA020703
Pays : United States
Organisme : Biomedical Laboratory Research and Development, VA Office of Research and Development
ID : BX004594
Pays : International
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