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The microbiota in cirrhosis and its role in hepatic decompensation

Research output: Contribution to journalReview articlepeer-review

Jonel Trebicka, Jane Macnaughtan, Bernd Schnabl, Debbie L Shawcross, Jasmohan S Bajaj

Original languageEnglish
Pages (from-to)S67-S81
JournalJournal of Hepatology
Volume75 Suppl 1
DOIs
PublishedJul 2021

Bibliographical note

Funding Information: J.T. is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57, P18 and CRC 1382, A09), European Union's Horizon 2020 Research and Innovation Programme (Galaxy, No. 668031 and MICROB-PREDICT, No. 825694) and Societal Challenges - Health, Demographic Change and Wellbeing (LIVERHOPE No. 731875), and Cellex Foundation (PREDICT). J.M. is supported by grants from the European Union's 2020 Research and Innovation Programme (CARBALIVE, No. 634579 and MICROB-PREDICT, No. 825694). B.S. was supported in part by services provided by NIH centers P30 DK120515 and P50 AA011999. D.L.S. is supported by grants from the European Union's Horizon 2020 Research and Innovation Programme (MICROB-PREDICT, No. 825694) and the National Institute for Health Research (PROFIT Trial No. PB-PG-0215-36070). J.S.B. was supported in part by VA Merit Review 2I0CX001076 and NCATS R21 TR002024 and R21TR003095. Funding Information: J.T. has received speaking and/or consulting fees from Gore, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis, and Martin Pharmaceutical. J.M. is a co-founder of Yaqrit Limited and has received speaker fees from Norgine and Yakult Europe. B.S. has been consulting for Ferring Research Institute, Intercept Pharmaceuticals, HOST Therabiomics, Mabwell Therapeutics and Patara Pharmaceuticals. B.S.’s institution UC San Diego has received grant support from BiomX, NGM Biopharmaceuticals, CymaBay Therapeutics, Synlogic Operating Company and Axial Biotherapeutics. D.L.S. has been consulting for Norgine, Kaleido Biosciences, Shionogi and Mallinckrodt Pharmaceuticals and has undertaken paid lectures for Norgine, Alfa Sigma and Falk Pharma. D.L.S’s institution King’s College London has received grant support from Norgine. J.S.B. has been an advisor to Valeant, Norgine, Kaleido and Takeda and his institution has received support from Bausch Health, Kaleido, Grifols and Mallinckrodt pharmaceuticals. Funding Information: J.T. is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57, P18 and CRC 1382, A09), European Union’s Horizon 2020 Research and Innovation Programme (Galaxy, No. 668031 and MICROB-PREDICT, No. 825694) and Societal Challenges - Health, Demographic Change and Wellbeing (LIVERHOPE No. 731875), and Cellex Foundation (PREDICT). J.M. is supported by grants from the European Union’s 2020 Research and Innovation Programme (CARBALIVE, No. 634579 and MICROB-PREDICT, No. 825694). B.S. was supported in part by services provided by NIH centers P30 DK120515 and P50 AA011999. D.L.S. is supported by grants from the European Union’s Horizon 2020 Research and Innovation Programme (MICROB-PREDICT, No. 825694) and the National Institute for Health Research (PROFIT Trial No. PB-PG-0215-36070). J.S.B. was supported in part by VA Merit Review 2I0CX001076 and NCATS R21 TR002024 and R21TR003095. Funding Information: This article is published as part of a supplement entitled New Concepts and Perspectives in Decompensated Cirrhosis. Publication of the supplement was supported financially by CSL Behring. The sponsor had no involvement in content development, the decision to submit the manuscript or in the acceptance of the manuscript for publication. Funding Information: This review is supported by MICROB-PREDICT project. The MICROB-PREDICT project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 825694. This reflects only the author’s view, and the European Commission is not responsible for any use that may be made of the information it contains. Publisher Copyright: © 2020 European Association for the Study of the Liver Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Cirrhosis - the common end-stage of chronic liver disease - is associated with a cascade of events, of which intestinal bacterial overgrowth and dysbiosis are central. Bacterial toxins entering the portal or systemic circulation can directly cause hepatocyte death, while dysbiosis also affects gut barrier function and increases bacterial translocation, leading to infections, systemic inflammation and vasodilation, which contribute to acute decompensation and organ failure. Acute decompensation and its severe forms, pre-acute-on-chronic liver failure (ACLF) and ACLF, are characterised by sudden organ dysfunction (and failure) and high short-term mortality. Patients with pre-ACLF and ACLF present with high-grade systemic inflammation, usually precipitated by proven bacterial infection and/or severe alcoholic hepatitis. However, no precipitant is identified in 30% of these patients, in whom bacterial translocation from the gut microbiota is assumed to be responsible for systemic inflammation and decompensation. Different microbiota profiles may influence the rate of decompensation and thereby outcome in these patients. Thus, targeting the microbiota is a promising strategy for the prevention and treatment of acute decompensation, pre-ACLF and ACLF. Approaches include the use of antibiotics such as rifaximin, faecal microbial transplantation and enterosorbents (e.g. Yaq-001), which bind microbial factors without exerting a direct effect on bacterial growth kinetics. This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.

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