Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury

  1. Schneider , Kai Markus ORCID logo
  2. Elfers, Carsten
  3. Ghallab, Ahmed ORCID logo
  4. Schneider, Carolin Victoria
  5. Galvez, Eric J.C.
  6. Mohs, Antje
  7. Gui, Wenfang
  8. Candels, Lena Susanna
  9. Wirtz, Theresa Hildegard
  10. Zuehlke, Sebastian
  11. Spiteller, Michael
  12. Myllys, Maiju ORCID logo
  13. Roulet, Alain ORCID logo
  14. Ouzerdine, Amirouche
  15. Lelouvier, Benjamin
  16. Kilic, Konrad
  17. Liao, Lijun
  18. Nier, Anika
  19. Latz, Eicke
  20. Bergheim, Ina
  21. Thaiss, Christoph A.
  22. Hengstler, Jan ORCID logo
  23. Strowig, Till
  24. Trautwein, Christian

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WeightNameValue
1000 Titel
  • Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury
1000 Autor/in
  1. Schneider , Kai Markus |
  2. Elfers, Carsten |
  3. Ghallab, Ahmed |
  4. Schneider, Carolin Victoria |
  5. Galvez, Eric J.C. |
  6. Mohs, Antje |
  7. Gui, Wenfang |
  8. Candels, Lena Susanna |
  9. Wirtz, Theresa Hildegard |
  10. Zuehlke, Sebastian |
  11. Spiteller, Michael |
  12. Myllys, Maiju |
  13. Roulet, Alain |
  14. Ouzerdine, Amirouche |
  15. Lelouvier, Benjamin |
  16. Kilic, Konrad |
  17. Liao, Lijun |
  18. Nier, Anika |
  19. Latz, Eicke |
  20. Bergheim, Ina |
  21. Thaiss, Christoph A. |
  22. Hengstler, Jan |
  23. Strowig, Till |
  24. Trautwein, Christian |
1000 Erscheinungsjahr 2020
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-11-13
1000 Erschienen in
1000 Quellenangabe
  • 11(4):909-933
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1016/j.jcmgh.2020.11.002 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900526/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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-/- mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF. 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-/- mice displayed exacerbated APAP- and LPS-induced liver injury, which was linked to significantly reduced gut and liver tissue microbiota diversity and correlated with increased intestinal permeability at baseline. Fecal microbiota transfer (FMT) from Nlrp6-/- mice into wild-type (WT) mice augmented liver injury on APAP treatment in recipient WT mice, resembling the inflammatory phenotype of Nlrp6-/- mice. Specifically, FMT skewed monocyte polarization in WT mice toward a Ly6Chi inflammatory phenotype, suggesting a critical function of these cells as sensors of gut-derived signals orchestrating the inflammatory response. 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.
1000 Sacherschließung
lokal Acute Liver Failure
lokal Gut-Liver-Axis
lokal Microbiota
lokal Dysbiosis
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-0047-3794|https://frl.publisso.de/adhoc/uri/RWxmZXJzLCBDYXJzdGVu|https://orcid.org/0000-0003-0695-3403|https://frl.publisso.de/adhoc/uri/U2NobmVpZGVyLCBDYXJvbGluIFZpY3Rvcmlh|https://frl.publisso.de/adhoc/uri/R2FsdmV6LCBFcmljIEouQy4=|https://frl.publisso.de/adhoc/uri/TW9ocywgQW50amU=|https://frl.publisso.de/adhoc/uri/R3VpLCBXZW5mYW5n|https://frl.publisso.de/adhoc/uri/Q2FuZGVscywgTGVuYSBTdXNhbm5h|https://frl.publisso.de/adhoc/uri/V2lydHosIFRoZXJlc2EgSGlsZGVnYXJk|https://frl.publisso.de/adhoc/uri/WnVlaGxrZSwgU2ViYXN0aWFu|https://frl.publisso.de/adhoc/uri/U3BpdGVsbGVyLCBNaWNoYWVs|https://orcid.org/0000-0001-9117-4572|https://orcid.org/0000-0002-2824-9954|https://frl.publisso.de/adhoc/uri/T3V6ZXJkaW5lLCBBbWlyb3VjaGU=|https://frl.publisso.de/adhoc/uri/TGVsb3V2aWVyLCBCZW5qYW1pbg==|https://frl.publisso.de/adhoc/uri/S2lsaWMsIEtvbnJhZA==|https://frl.publisso.de/adhoc/uri/TGlhbywgTGlqdW4=|https://frl.publisso.de/adhoc/uri/TmllciwgQW5pa2E=|https://frl.publisso.de/adhoc/uri/TGF0eiwgRWlja2U=|https://frl.publisso.de/adhoc/uri/QmVyZ2hlaW0sIEluYQ==|https://frl.publisso.de/adhoc/uri/VGhhaXNzLCBDaHJpc3RvcGggQS4=|https://orcid.org/0000-0002-1427-5246|https://frl.publisso.de/adhoc/uri/U3Ryb3dpZywgVGlsbA==|https://frl.publisso.de/adhoc/uri/VHJhdXR3ZWluLCBDaHJpc3RpYW4=
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Bundesministerium für Bildung und Forschung |
  3. Interdisciplinary Centre for Clinical Research |
  4. Helmholtz Association |
  5. Studienstiftung des Deutschen Volkes |
1000 Fördernummer
  1. CRC1382; SFB/TRR 57; TR285/10-2; SCHN 1626/1-1
  2. 01KU1214A; FKZ 031L0052; 031L0045
  3. 691438
  4. VH-NG-933
  5. -
1000 Förderprogramm
  1. -
  2. ObiHep grant; Liver-LiSyM grant; HDHL-INTIMIC Di-Mi-Liv
  3. START
  4. -
  5. -
1000 Dateien
  1. Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury
    Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer CRC1382; SFB/TRR 57; TR285/10-2; SCHN 1626/1-1
  2. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm ObiHep grant; Liver-LiSyM grant; HDHL-INTIMIC Di-Mi-Liv
    1000 Fördernummer 01KU1214A; FKZ 031L0052; 031L0045
  3. 1000 joinedFunding-child
    1000 Förderer Interdisciplinary Centre for Clinical Research |
    1000 Förderprogramm START
    1000 Fördernummer 691438
  4. 1000 joinedFunding-child
    1000 Förderer Helmholtz Association |
    1000 Förderprogramm -
    1000 Fördernummer VH-NG-933
  5. 1000 joinedFunding-child
    1000 Förderer Studienstiftung des Deutschen Volkes |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6429545.rdf
1000 Erstellt am 2021-09-28T13:36:02.381+0200
1000 Erstellt von 254
1000 beschreibt frl:6429545
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2021-10-01T08:38:52.395+0200
1000 Objekt bearb. Thu Sep 30 13:59:55 CEST 2021
1000 Vgl. frl:6429545
1000 Oai Id
  1. oai:frl.publisso.de:frl:6429545 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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