Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury.
Acetaminophen
/ toxicity
Analgesics, Non-Narcotic
/ toxicity
Animals
Chemical and Drug Induced Liver Injury
/ etiology
Disease Models, Animal
Dysbiosis
/ complications
Female
Gastrointestinal Microbiome
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Permeability
Receptors, Cell Surface
/ physiology
Acute Liver Failure
Dysbiosis
Gut-Liver-Axis
Microbiota
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2021
2021
Historique:
received:
02
06
2020
revised:
31
10
2020
accepted:
02
11
2020
pubmed:
16
11
2020
medline:
8
3
2022
entrez:
15
11
2020
Statut:
ppublish
Résumé
Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF. To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK BioBank population-based cohort. For functional studies, male Nlrp6 Multivariate Cox regression analyses revealed a significantly increased risk (odds ratio, 2.3-3) for developing ALF in UK BioBank participants with PPI or ABx. Similarly, dysbiotic Nlrp6 Our data show an important yet unknown function of intestinal microbiota during ALF. Intestinal dysbiosis was transferrable to healthy WT mice via FMT and aggravated liver injury. Our study highlights intestinal microbiota as a targetable risk factor for ALF.
Sections du résumé
BACKGROUND & AIMS
Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF.
METHODS
To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK BioBank population-based cohort. For functional studies, male Nlrp6
RESULTS
Multivariate Cox regression analyses revealed a significantly increased risk (odds ratio, 2.3-3) for developing ALF in UK BioBank participants with PPI or ABx. Similarly, dysbiotic Nlrp6
CONCLUSIONS
Our data show an important yet unknown function of intestinal microbiota during ALF. Intestinal dysbiosis was transferrable to healthy WT mice via FMT and aggravated liver injury. Our study highlights intestinal microbiota as a targetable risk factor for ALF.
Identifiants
pubmed: 33189892
pii: S2352-345X(20)30181-8
doi: 10.1016/j.jcmgh.2020.11.002
pmc: PMC7900526
pii:
doi:
Substances chimiques
Analgesics, Non-Narcotic
0
Nod-like receptor pyrin domain-containing protein 6, mouse
0
Receptors, Cell Surface
0
Acetaminophen
362O9ITL9D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
909-933Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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