Intestinal Virome in Patients With Alcoholic Hepatitis.
Adult
Aged
Animals
Bacteriophages
/ genetics
Case-Control Studies
DNA, Viral
/ isolation & purification
End Stage Liver Disease
/ diagnosis
Feces
/ virology
Female
Hepatitis, Alcoholic
/ diagnosis
Herpesviridae
/ genetics
Humans
Intestinal Mucosa
/ virology
Liver
/ pathology
Liver Cirrhosis
/ diagnosis
Male
Metagenomics
Middle Aged
Parvoviridae
/ genetics
RNA, Viral
/ isolation & purification
Severity of Illness Index
Survival Rate
Virome
/ genetics
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
06
05
2020
revised:
15
06
2020
accepted:
17
06
2020
pubmed:
13
7
2020
medline:
5
5
2021
entrez:
13
7
2020
Statut:
ppublish
Résumé
Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD. We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality. In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
Sections du résumé
BACKGROUND AND AIMS
Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.
APPROACH AND RESULTS
We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality.
CONCLUSIONS
In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
Identifiants
pubmed: 32654263
doi: 10.1002/hep.31459
pmc: PMC8159727
mid: NIHMS1702587
doi:
Substances chimiques
DNA, Viral
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2182-2196Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA020703
Pays : United States
Organisme : BLRD VA
ID : I01 BX004594
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120515
Pays : United States
Organisme : BLRD VA
ID : BX004594
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA011999
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA026939
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA24726
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01AA020703
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA024726
Pays : United States
Informations de copyright
© 2020 by the American Association for the Study of Liver Diseases.
Références
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4485-93
pubmed: 25288760
Appl Environ Microbiol. 2009 Dec;75(23):7537-41
pubmed: 19801464
Hepatology. 2020 Feb;71(2):522-538
pubmed: 31228214
Dig Liver Dis. 2015 Dec;47(12):1007-12
pubmed: 26257129
Sci Rep. 2017 Jan 04;7:39642
pubmed: 28051127
Autoimmun Rev. 2004 Jan;3(1):61-9
pubmed: 14871651
Dig Dis Sci. 2019 Jul;64(7):1878-1892
pubmed: 31076986
Bioinformatics. 2018 Apr 1;34(7):1235-1237
pubmed: 29194469
ISME J. 2017 Jul;11(7):1511-1520
pubmed: 28291233
J Hepatol. 2013 Mar;58(3):593-608
pubmed: 23419824
Bioinformatics. 2018 Dec 15;34(24):4287-4289
pubmed: 29982281
Cell. 2014 Mar 27;157(1):142-50
pubmed: 24679532
J Hepatol. 2018 Mar;68(3):511-518
pubmed: 29175535
Alcohol Clin Exp Res. 2014 Jun;38(6):1489-501
pubmed: 24890666
J Hepatol. 2018 Aug;69(2):396-405
pubmed: 29654817
J Hepatol. 2012;56 Suppl 1:S39-45
pubmed: 22300464
N Engl J Med. 2015 Apr 23;372(17):1619-28
pubmed: 25901427
Cell. 2009 Jul 10;138(1):30-50
pubmed: 19596234
World J Gastroenterol. 2015 Nov 28;21(44):12667-75
pubmed: 26640344
J Pediatr Gastroenterol Nutr. 2019 Jan;68(1):30-36
pubmed: 30169455
Hepatology. 2020 Jul;72(1):271-286
pubmed: 32056227
J Hepatol. 2020 Mar;72(3):391-400
pubmed: 31606552
N Engl J Med. 2009 Jun 25;360(26):2758-69
pubmed: 19553649
World J Gastroenterol. 2015 Nov 14;21(42):11904-13
pubmed: 26576079
Methods Mol Biol. 2018;1838:85-95
pubmed: 30128991
mBio. 2018 Nov 20;9(6):
pubmed: 30459201
Front Microbiol. 2016 Sep 08;7:1352
pubmed: 27660623
Microbiol Mol Biol Rev. 2000 Mar;64(1):69-114
pubmed: 10704475
J Clin Microbiol. 1999 Sep;37(9):2852-7
pubmed: 10449464
BMC Gastroenterol. 2019 Jun 18;19(1):94
pubmed: 31215410
Virol J. 2010 Sep 22;7:252
pubmed: 20860842
Pediatr Transplant. 2002 Dec;6(6):456-64
pubmed: 12453197
Gut. 2019 Jul;68(7):1169-1179
pubmed: 30842211
Gut. 2016 May;65(5):830-9
pubmed: 26642859
In Vivo. 2003 Jan-Feb;17(1):29-33
pubmed: 12655786
Nature. 2019 Nov;575(7783):505-511
pubmed: 31723265
Cell. 2015 Jan 29;160(3):447-60
pubmed: 25619688
Genome Res. 2002 Apr;12(4):656-64
pubmed: 11932250
Clin Gastroenterol Hepatol. 2017 Apr;15(4):600-602
pubmed: 27816755
Liver. 1994 Feb;14(1):1-13
pubmed: 8177024
Genome Biol. 2011 Jun 24;12(6):R60
pubmed: 21702898
Am J Clin Pathol. 2008 Aug;130(2):231-7
pubmed: 18628092
Am J Surg Pathol. 1990 Jun;14(6):538-47
pubmed: 2159731
Pathology. 2019 Jan;51(1):86-90
pubmed: 30497802
NPJ Biofilms Microbiomes. 2016 Jul 06;2:16010
pubmed: 28721247
Front Physiol. 2020 Apr 24;11:370
pubmed: 32390870
Cell Host Microbe. 2019 Oct 9;26(4):527-541.e5
pubmed: 31600503
Gastroenterology. 2018 Aug;155(2):529-541.e5
pubmed: 29689266
Cell Host Microbe. 2019 Dec 11;26(6):764-778.e5
pubmed: 31757768
J Abnorm Psychol. 1997 Nov;106(4):545-53
pubmed: 9358685
Nat Biotechnol. 2011 May;29(5):393-6
pubmed: 21552235
Hepatology. 2006 Jun;43(6):1317-25
pubmed: 16729309
Trends Microbiol. 2014 Jul;22(7):399-405
pubmed: 24656964
Adv Virus Res. 2019;103:33-70
pubmed: 30635077