{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:48:40Z","timestamp":1793998120424,"version":"4.8.0"},"reference-count":169,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1038\/s41575-020-00376-3","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T16:03:25Z","timestamp":1606752205000},"page":"167-180","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":201,"title":["Utilizing the gut microbiome in decompensated cirrhosis and acute-on-chronic liver failure"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-3881","authenticated-orcid":false,"given":"Jonel","family":"Trebicka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2627-833X","authenticated-orcid":false,"given":"Peer","family":"Bork","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-4932","authenticated-orcid":false,"given":"Aleksander","family":"Krag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0886-9101","authenticated-orcid":false,"given":"Manimozhiyan","family":"Arumugam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"376_CR1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cell.2016.01.013","volume":"164","author":"R Sender","year":"2016","unstructured":"Sender, R., Fuchs, S. & Milo, R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cell humans. Cell 164, 337\u2013340 (2016).","journal-title":"Cell"},{"key":"376_CR2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1002533","volume":"14","author":"R Sender","year":"2016","unstructured":"Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14, e1002533 (2016).","journal-title":"PLoS Biol."},{"key":"376_CR3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","volume":"464","author":"J Qin","year":"2010","unstructured":"Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59\u201365 (2010).","journal-title":"Nature"},{"key":"376_CR4","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nbt.2942","volume":"32","author":"J Li","year":"2014","unstructured":"Li, J. et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32, 834\u2013841 (2014).","journal-title":"Nat. Biotechnol."},{"key":"376_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0603-3","author":"A Almeida","year":"2020","unstructured":"Almeida, A. et al. A unified catalog of 204,938 reference genomes from the human gut microbiome. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-020-0603-3 (2020).","journal-title":"Nat. Biotechnol."},{"key":"376_CR6","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","volume":"375","author":"SV Lynch","year":"2016","unstructured":"Lynch, S. V. & Pedersen, O. The human intestinal microbiome in health and disease. N. Engl. J. Med. 375, 2369\u20132379 (2016).","journal-title":"N. Engl. J. Med."},{"key":"376_CR7","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1159\/000371678","volume":"33","author":"JM Ridlon","year":"2015","unstructured":"Ridlon, J. M., Kang, D. J., Hylemon, P. B. & Bajaj, J. S. Gut microbiota, cirrhosis, and alcohol regulate bile acid metabolism in the gut. Dig. Dis. 33, 338\u2013345 (2015).","journal-title":"Dig. Dis."},{"key":"376_CR8","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1136\/gutjnl-2016-312729","volume":"65","author":"H Tilg","year":"2016","unstructured":"Tilg, H., Cani, P. D. & Mayer, E. A. Gut microbiome and liver diseases. Gut 65, 2035\u20132044 (2016).","journal-title":"Gut"},{"key":"376_CR9","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41575-018-0011-z","volume":"15","author":"A Tripathi","year":"2018","unstructured":"Tripathi, A. et al. The gut\u2013liver axis and the intersection with the microbiome. Nat. Rev. Gastroenterol. Hepatol. 15, 397\u2013411 (2018).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"376_CR10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","volume":"14","author":"T Tsuchida","year":"2017","unstructured":"Tsuchida, T. & Friedman, S. L. Mechanisms of hepatic stellate cell activation. Nat. Rev. Gastroenterol. Hepatol. 14, 397\u2013411 (2017).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"376_CR11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","volume":"65","author":"M Parola","year":"2019","unstructured":"Parola, M. & Pinzani, M. Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues. Mol. Aspects Med. 65, 37\u201355 (2019).","journal-title":"Mol. Aspects Med."},{"key":"376_CR12","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(14)60121-5","volume":"383","author":"EA Tsochatzis","year":"2014","unstructured":"Tsochatzis, E. A., Bosch, J. & Burroughs, A. K. Liver cirrhosis. Lancet 383, 1749\u20131761 (2014).","journal-title":"Lancet"},{"key":"376_CR13","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/gut.11.5.420","volume":"11","author":"ZR Vlahcevic","year":"1970","unstructured":"Vlahcevic, Z. R., Buhac, I., Bell, C. C. Jr & Swell, L. Abnormal metabolism of secondary bile acids in patients with cirrhosis. Gut 11, 420\u2013422 (1970).","journal-title":"Gut"},{"key":"376_CR14","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.94416","volume":"2","author":"C Acharya","year":"2017","unstructured":"Acharya, C., Sahingur, S. E. & Bajaj, J. S. Microbiota, cirrhosis, and the emerging oral\u2013gut\u2013liver axis. JCI Insight 2, e94416 (2017).","journal-title":"JCI Insight"},{"key":"376_CR15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0168-8278(00)80422-5","volume":"32","author":"J Bosch","year":"2000","unstructured":"Bosch, J. & Garcia-Pagan, J. C. Complications of cirrhosis. I. Portal hypertension. J. Hepatol. 32, 141\u2013156 (2000).","journal-title":"J. Hepatol."},{"key":"376_CR16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jhep.2018.03.024","volume":"69","author":"European Association for the Study of the Liver","year":"2018","unstructured":"European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J. Hepatol. 69, 406\u2013460 (2018).","journal-title":"J. Hepatol."},{"key":"376_CR17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature13568","volume":"513","author":"N Qin","year":"2014","unstructured":"Qin, N. et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 513, 59\u201364 (2014).","journal-title":"Nature"},{"key":"376_CR18","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/hep.28740","volume":"64","author":"J Claria","year":"2016","unstructured":"Claria, J. et al. Systemic inflammation in decompensated cirrhosis: characterization and role in acute-on-chronic liver failure. Hepatology 64, 1249\u20131264 (2016).","journal-title":"Hepatology"},{"key":"376_CR19","doi-asserted-by":"crossref","first-page":"476","DOI":"10.3389\/fimmu.2019.00476","volume":"10","author":"J Trebicka","year":"2019","unstructured":"Trebicka, J. et al. Addressing profiles of systemic inflammation across the different clinical phenotypes of acutely decompensated cirrhosis. Front. Immunol. 10, 476 (2019).","journal-title":"Front. Immunol."},{"key":"376_CR20","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1053\/j.gastro.2013.02.042","volume":"144","author":"R Moreau","year":"2013","unstructured":"Moreau, R. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144, 1426\u20131437 (2013).","journal-title":"Gastroenterology"},{"key":"376_CR21","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1136\/gutjnl-2017-314240","volume":"67","author":"J Fernandez","year":"2018","unstructured":"Fernandez, J. et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut 67, 1870\u20131880 (2018).","journal-title":"Gut"},{"key":"376_CR22","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.07.019","author":"JS Bajaj","year":"2020","unstructured":"Bajaj, J. S. et al. Serum levels of metabolites produced by intestinal microbes and lipid moieties independently associated with acute on chronic liver failure and death in patients with cirrhosis. Gastroenterology https:\/\/doi.org\/10.1053\/j.gastro.2020.07.019 (2020).","journal-title":"Gastroenterology"},{"key":"376_CR23","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41575-018-0099-1","volume":"16","author":"JS Bajaj","year":"2019","unstructured":"Bajaj, J. S. Alcohol, liver disease and the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 16, 235\u2013246 (2019).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"376_CR24","volume":"12","author":"P Byass","year":"2014","unstructured":"Byass, P. The global burden of liver disease: a challenge for methods and for public health. BMC Med. 12, 159 (2014).","journal-title":"BMC Med."},{"key":"376_CR25","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S2468-1253(16)30081-4","volume":"1","author":"P Gines","year":"2016","unstructured":"Gines, P. et al. Screening for liver fibrosis in the general population: a call for action. Lancet Gastroenterol. Hepatol. 1, 256\u2013260 (2016).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"376_CR26","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S2468-1253(19)30349-8","volume":"5","author":"GBDC Collaborators","year":"2020","unstructured":"Collaborators, G. B. D. C. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 5, 245\u2013266 (2020).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"376_CR27","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.jhep.2016.06.018","volume":"65","author":"E Stein","year":"2016","unstructured":"Stein, E. et al. Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide. J. Hepatol. 65, 998\u20131005 (2016).","journal-title":"J. Hepatol."},{"key":"376_CR28","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1053\/j.gastro.2018.07.008","volume":"155","author":"D Kim","year":"2018","unstructured":"Kim, D. et al. Changing trends in etiology-based annual mortality from chronic liver disease, from 2007 through 2016. Gastroenterology 155, 1154\u20131163.e3 (2018).","journal-title":"Gastroenterology"},{"key":"376_CR29","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jhep.2019.01.003","volume":"70","author":"SP Singh","year":"2019","unstructured":"Singh, S. P., Panigrahi, S., Mishra, D. & Khatua, C. R. Alcohol-associated liver disease, not hepatitis B, is the major cause of cirrhosis in Asia. J. Hepatol. 70, 1031\u20131032 (2019).","journal-title":"J. Hepatol."},{"key":"376_CR30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1055\/s-0036-1583201","volume":"36","author":"AM Allen","year":"2016","unstructured":"Allen, A. M. & Kim, W. R. Epidemiology and healthcare burden of acute-on-chronic liver failure. Semin. Liver Dis. 36, 123\u2013126 (2016).","journal-title":"Semin. Liver Dis."},{"key":"376_CR31","unstructured":"Zutshi, Y. Liver Disease Treatments: The Global Market (BCC, 2015)."},{"key":"376_CR32","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1056\/NEJMra1504367","volume":"375","author":"PS Ge","year":"2016","unstructured":"Ge, P. S. & Runyon, B. A. Treatment of patients with cirrhosis. N. Engl. J. Med. 375, 767\u2013777 (2016).","journal-title":"N. Engl. J. Med."},{"key":"376_CR33","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1056\/NEJMra1914900","volume":"382","author":"V Arroyo","year":"2020","unstructured":"Arroyo, V., Moreau, R. & Jalan, R. Acute-on-chronic liver failure. N. Engl. J. Med. 382, 2137\u20132145 (2020).","journal-title":"N. Engl. J. Med."},{"key":"376_CR34","doi-asserted-by":"crossref","first-page":"16041","DOI":"10.1038\/nrdp.2016.41","volume":"2","author":"V Arroyo","year":"2016","unstructured":"Arroyo, V. et al. Acute-on-chronic liver failure in cirrhosis. Nat. Rev. Dis. Primers 2, 16041 (2016).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"376_CR35","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jhep.2020.06.013","volume":"73","author":"J Trebicka","year":"2020","unstructured":"Trebicka, J. et al. The PREDICT study uncovers three clinical courses in acutely decompensated cirrhosis with distinct pathophysiology. J. Hepatol. 73, 842\u2013854 (2020).","journal-title":"J. Hepatol."},{"key":"376_CR36","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s12072-014-9580-2","volume":"8","author":"SK Sarin","year":"2014","unstructured":"Sarin, S. K. et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol. Int. 8, 453\u2013471 (2014).","journal-title":"Hepatol. Int."},{"key":"376_CR37","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/hep.27077","volume":"60","author":"JS Bajaj","year":"2014","unstructured":"Bajaj, J. S. et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 60, 250\u2013256 (2014).","journal-title":"Hepatology"},{"key":"376_CR38","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1002\/hep.29773","volume":"67","author":"JG O\u2019Leary","year":"2018","unstructured":"O\u2019Leary, J. G. et al. NACSELD acute-on-chronic liver failure (NACSELD-ACLF) score predicts 30-day survival in hospitalized patients with cirrhosis. Hepatology 67, 2367\u20132374 (2018).","journal-title":"Hepatology"},{"key":"376_CR39","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1136\/gutjnl-2016-312670","volume":"66","author":"R Hernaez","year":"2017","unstructured":"Hernaez, R., Sola, E., Moreau, R. & Gines, P. Acute-on-chronic liver failure: an update. Gut 66, 541\u2013553 (2017).","journal-title":"Gut"},{"key":"376_CR40","volume":"11","author":"TY Kim","year":"2016","unstructured":"Kim, T. Y. et al. Characteristics and discrepancies in acute-on-chronic liver failure: need for a unified definition. PLoS ONE 11, e0146745 (2016).","journal-title":"PLoS ONE"},{"key":"376_CR41","volume":"6","author":"H Li","year":"2016","unstructured":"Li, H. et al. Characteristics, diagnosis and prognosis of acute-on-chronic liver failure in cirrhosis associated to hepatitis B. Sci. Rep. 6, 25487 (2016).","journal-title":"Sci. Rep."},{"key":"376_CR42","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/hep.1840170622","volume":"17","author":"G Garcia-Tsao","year":"1993","unstructured":"Garcia-Tsao, G., Albillos, A., Barden, G. E. & West, A. B. Bacterial translocation in acute and chronic portal hypertension. Hepatology 17, 1081\u20131085 (1993).","journal-title":"Hepatology"},{"key":"376_CR43","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.cmet.2020.06.005","volume":"32","author":"TG Oh","year":"2020","unstructured":"Oh, T. G. et al. A universal gut-microbiome-derived signature predicts cirrhosis. Cell Metab. 32, 878\u2013888.e6 (2020).","journal-title":"Cell Metab."},{"key":"376_CR44","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1101\/gr.233940.117","volume":"28","author":"K Korpela","year":"2018","unstructured":"Korpela, K. et al. Selective maternal seeding and environment shape the human gut microbiome. Genome Res. 28, 561\u2013568 (2018).","journal-title":"Genome Res."},{"key":"376_CR45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.gtc.2016.09.013","volume":"46","author":"C Acharya","year":"2017","unstructured":"Acharya, C. & Bajaj, J. S. Gut microbiota and complications of liver disease. Gastroenterol. Clin. North Am. 46, 155\u2013169 (2017).","journal-title":"Gastroenterol. Clin. North Am."},{"key":"376_CR46","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1055\/s-0037-1602763","volume":"37","author":"BC Davis","year":"2017","unstructured":"Davis, B. C. & Bajaj, J. S. The human gut microbiome in liver diseases. Semin. Liver Dis. 37, 128\u2013140 (2017).","journal-title":"Semin. Liver Dis."},{"key":"376_CR47","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","volume":"72","author":"A Albillos","year":"2020","unstructured":"Albillos, A., Gottardi, A. & Rescigno, M. The gut\u2013liver axis in liver disease: pathophysiological basis for therapy. J. Hepatol. 72, 558\u2013577 (2020).","journal-title":"J. Hepatol."},{"key":"376_CR48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/hep.26321","volume":"58","author":"P Hartmann","year":"2013","unstructured":"Hartmann, P. et al. Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology 58, 108\u2013119 (2013).","journal-title":"Hepatology"},{"key":"376_CR49","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S0168-8278(98)80022-6","volume":"29","author":"JH Henriksen","year":"1998","unstructured":"Henriksen, J. H., Moller, S., Ring-Larsen, H. & Christensen, N. J. The sympathetic nervous system in liver disease. J. Hepatol. 29, 328\u2013341 (1998).","journal-title":"J. Hepatol."},{"key":"376_CR50","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jhep.2017.05.007","volume":"67","author":"R Wiest","year":"2017","unstructured":"Wiest, R., Albillos, A., Trauner, M., Bajaj, J. S. & Jalan, R. Targeting the gut\u2013liver axis in liver disease. J. Hepatol. 67, 1084\u20131103 (2017).","journal-title":"J. Hepatol."},{"key":"376_CR51","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/hep.24789","volume":"55","author":"Z Teltschik","year":"2012","unstructured":"Teltschik, Z. et al. Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense. Hepatology 55, 1154\u20131163 (2012).","journal-title":"Hepatology"},{"key":"376_CR52","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.chom.2016.01.003","volume":"19","author":"L Wang","year":"2016","unstructured":"Wang, L. et al. Intestinal REG3 lectins protect against alcoholic steatohepatitis by reducing mucosa-associated microbiota and preventing bacterial translocation. Cell Host Microbe 19, 227\u2013239 (2016).","journal-title":"Cell Host Microbe"},{"key":"376_CR53","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.jhep.2013.01.038","volume":"58","author":"J Du Plessis","year":"2013","unstructured":"Du Plessis, J. et al. Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function. J. Hepatol. 58, 1125\u20131132 (2013).","journal-title":"J. Hepatol."},{"key":"376_CR54","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/hep.30349","volume":"70","author":"L Munoz","year":"2019","unstructured":"Munoz, L. et al. Intestinal immune dysregulation driven by dysbiosis promotes barrier disruption and bacterial translocation in rats with cirrhosis. Hepatology 70, 925\u2013938 (2019).","journal-title":"Hepatology"},{"key":"376_CR55","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0083341","volume":"8","author":"J Trebicka","year":"2013","unstructured":"Trebicka, J. et al. Soluble TNF-\u03b1-receptors I are prognostic markers in TIPS-treated patients with cirrhosis and portal hypertension. PLoS ONE 8, e83341 (2013).","journal-title":"PLoS ONE"},{"key":"376_CR56","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1136\/gutjnl-2019-319044","volume":"69","author":"A Queck","year":"2020","unstructured":"Queck, A. et al. Role of portal venous platelet activation in patients with decompensated cirrhosis and TIPS. Gut 69, 1535\u20131536 (2020).","journal-title":"Gut"},{"key":"376_CR57","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/gutjnl-2018-316227","volume":"68","author":"R Schierwagen","year":"2019","unstructured":"Schierwagen, R. et al. Circulating microbiome in blood of different circulatory compartments. Gut 68, 578\u2013580 (2019).","journal-title":"Gut"},{"key":"376_CR58","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.jhep.2013.12.019","volume":"60","author":"JS Bajaj","year":"2014","unstructured":"Bajaj, J. S. et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J. Hepatol. 60, 940\u2013947 (2014).","journal-title":"J. Hepatol."},{"key":"376_CR59","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1111\/liv.14097","volume":"39","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y. et al. Characterization of the circulating microbiome in acute-on-chronic liver failure associated with hepatitis B. Liver Int. 39, 1207\u20131216 (2019).","journal-title":"Liver Int."},{"key":"376_CR60","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1053\/j.gastro.2012.07.018","volume":"143","author":"E Villa","year":"2012","unstructured":"Villa, E. et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 143, 1253\u20131260 (2012).","journal-title":"Gastroenterology"},{"key":"376_CR61","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.27546","volume":"61","author":"F Nery","year":"2015","unstructured":"Nery, F. et al. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 61, 660\u2013667 (2015).","journal-title":"Hepatology"},{"key":"376_CR62","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/0016-5085(95)90147-7","volume":"108","author":"G Garcia-Tsao","year":"1995","unstructured":"Garcia-Tsao, G., Lee, F. Y., Barden, G. E., Cartun, R. & West, A. B. Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites. Gastroenterology 108, 1835\u20131841 (1995).","journal-title":"Gastroenterology"},{"key":"376_CR63","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1002\/hep.29581","volume":"67","author":"S Macdonald","year":"2018","unstructured":"Macdonald, S. et al. Cell death markers in patients with cirrhosis and acute decompensation. Hepatology 67, 989\u20131002 (2018).","journal-title":"Hepatology"},{"key":"376_CR64","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/hep4.1135","volume":"2","author":"M Praktiknjo","year":"2018","unstructured":"Praktiknjo, M. et al. Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis. Hepatol. Commun. 2, 211\u2013222 (2018).","journal-title":"Hepatol. Commun."},{"key":"376_CR65","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/hep.27795","volume":"62","author":"Y Shi","year":"2015","unstructured":"Shi, Y. et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 62, 232\u2013242 (2015).","journal-title":"Hepatology"},{"key":"376_CR66","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrgastro.2015.219","volume":"13","author":"SK Sarin","year":"2016","unstructured":"Sarin, S. K. & Choudhury, A. Acute-on-chronic liver failure: terminology, mechanisms and management. Nat. Rev. Gastroenterol. Hepatol. 13, 131\u2013149 (2016).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"376_CR67","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2010.03.006","volume":"140","author":"R Medzhitov","year":"2010","unstructured":"Medzhitov, R. Inflammation 2010: new adventures of an old flame. Cell 140, 771\u2013776 (2010).","journal-title":"Cell"},{"key":"376_CR68","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jhep.2019.11.009","volume":"72","author":"R Moreau","year":"2020","unstructured":"Moreau, R. et al. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF. J. Hepatol. 72, 688\u2013701 (2020).","journal-title":"J. Hepatol."},{"key":"376_CR69","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/liv.13610","volume":"38","author":"JM Lehmann","year":"2018","unstructured":"Lehmann, J. M. et al. Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality. Liver Int. 38, 875\u2013884 (2018).","journal-title":"Liver Int."},{"key":"376_CR70","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41586-019-1742-x","volume":"575","author":"Y Duan","year":"2019","unstructured":"Duan, Y. et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 575, 505\u2013511 (2019).","journal-title":"Nature"},{"key":"376_CR71","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2015-310585","volume":"65","author":"M Llopis","year":"2016","unstructured":"Llopis, M. et al. Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease. Gut 65, 830\u2013839 (2016).","journal-title":"Gut"},{"key":"376_CR72","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/hep.29623","volume":"67","author":"P Puri","year":"2018","unstructured":"Puri, P. et al. The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis. Hepatology 67, 1284\u20131302 (2018).","journal-title":"Hepatology"},{"key":"376_CR73","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/hep4.1308","volume":"3","author":"C Jansen","year":"2019","unstructured":"Jansen, C. et al. Left ventricular longitudinal contractility predicts acute-on-chronic liver failure development and mortality after transjugular intrahepatic portosystemic shunt. Hepatol. Commun. 3, 340\u2013347 (2019).","journal-title":"Hepatol. Commun."},{"key":"376_CR74","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jhep.2016.10.025","volume":"66","author":"J Trebicka","year":"2017","unstructured":"Trebicka, J. Emergency TIPS in a Child\u2013Pugh B patient: when does the window of opportunity open and close? J. Hepatol. 66, 442\u2013450 (2017).","journal-title":"J. Hepatol."},{"key":"376_CR75","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1055\/s-0036-1583195","volume":"36","author":"J Trebicka","year":"2016","unstructured":"Trebicka, J. Predisposing factors in acute-on-chronic liver failure. Semin. Liver Dis. 36, 167\u2013173 (2016).","journal-title":"Semin. Liver Dis."},{"key":"376_CR76","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1002\/hep.29612","volume":"67","author":"C Jansen","year":"2018","unstructured":"Jansen, C. et al. Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality. Hepatology 67, 1472\u20131484 (2018).","journal-title":"Hepatology"},{"key":"376_CR77","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jhep.2005.10.013","volume":"44","author":"G D\u2019Amico","year":"2006","unstructured":"D\u2019Amico, G., Garcia-Tsao, G. & Pagliaro, L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J. Hepatol. 44, 217\u2013231 (2006).","journal-title":"J. Hepatol."},{"key":"376_CR78","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jhep.2010.06.042","volume":"54","author":"R Jalan","year":"2011","unstructured":"Jalan, R. et al. Acute endotoxemia following transjugular intrahepatic stent-shunt insertion is associated with systemic and cerebral vasodilatation with increased whole body nitric oxide production in critically ill cirrhotic patients. J. Hepatol. 54, 265\u2013271 (2011).","journal-title":"J. Hepatol."},{"key":"376_CR79","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0096864","volume":"9","author":"S Bala","year":"2014","unstructured":"Bala, S., Marcos, M., Gattu, A., Catalano, D. & Szabo, G. Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS ONE 9, e96864 (2014).","journal-title":"PLoS ONE"},{"key":"376_CR80","doi-asserted-by":"crossref","first-page":"G131","DOI":"10.1152\/ajpgi.00103.2017","volume":"314","author":"RM Voigt","year":"2018","unstructured":"Voigt, R. M. et al. Diurnal variations in intestinal barrier integrity and liver pathology in mice: implications for alcohol binge. Am. J. Physiol. Gastrointest. Liver Physiol. 314, G131\u2013G141 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"376_CR81","doi-asserted-by":"crossref","first-page":"G966","DOI":"10.1152\/ajpgi.00380.2011","volume":"302","author":"EA Mutlu","year":"2012","unstructured":"Mutlu, E. A. et al. Colonic microbiome is altered in alcoholism. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G966\u2013G978 (2012).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"376_CR82","doi-asserted-by":"crossref","DOI":"10.1186\/s40168-017-0359-2","volume":"5","author":"VB Dubinkina","year":"2017","unstructured":"Dubinkina, V. B. et al. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease. Microbiome 5, 141 (2017).","journal-title":"Microbiome"},{"key":"376_CR83","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0140-6736(84)92109-3","volume":"1","author":"I Bjarnason","year":"1984","unstructured":"Bjarnason, I., Peters, T. J. & Wise, R. J. The leaky gut of alcoholism: possible route of entry for toxic compounds. Lancet 1, 179\u2013182 (1984).","journal-title":"Lancet"},{"key":"376_CR84","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1172\/JCI90562","volume":"127","author":"AM Yang","year":"2017","unstructured":"Yang, A. M. et al. Intestinal fungi contribute to development of alcoholic liver disease. J. Clin. Invest. 127, 2829\u20132841 (2017).","journal-title":"J. Clin. Invest."},{"key":"376_CR85","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1136\/gutjnl-2016-313170","volume":"67","author":"JS Bajaj","year":"2018","unstructured":"Bajaj, J. S. et al. Fungal dysbiosis in cirrhosis. Gut 67, 1146\u20131154 (2018).","journal-title":"Gut"},{"key":"376_CR86","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/S0140-6736(04)16206-5","volume":"363","author":"A Albillos","year":"2004","unstructured":"Albillos, A., de-la-Hera, A. & Alvarez-Mon, M. Serum lipopolysaccharide-binding protein prediction of severe bacterial infection in cirrhotic patients with ascites. Lancet 363, 1608\u20131610 (2004).","journal-title":"Lancet"},{"key":"376_CR87","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jhep.2019.11.009","volume":"72","author":"R Moreau","year":"2020","unstructured":"Moreau, R. et al. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF. J. Hepatol. 72, 688\u2013701 (2020).","journal-title":"J. Hepatol."},{"key":"376_CR88","doi-asserted-by":"crossref","first-page":"382","DOI":"10.4161\/gmic.25723","volume":"4","author":"JM Ridlon","year":"2013","unstructured":"Ridlon, J. M., Alves, J. M., Hylemon, P. B. & Bajaj, J. S. Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship. Gut Microbes 4, 382\u2013387 (2013).","journal-title":"Gut Microbes"},{"key":"376_CR89","doi-asserted-by":"crossref","first-page":"G929","DOI":"10.1152\/ajpgi.00315.2013","volume":"306","author":"G Kakiyama","year":"2014","unstructured":"Kakiyama, G. et al. Colonic inflammation and secondary bile acids in alcoholic cirrhosis. Am. J. Physiol. Gastrointest. Liver Physiol. 306, G929\u2013G937 (2014).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"376_CR90","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ajpath.2014.10.009","volume":"185","author":"L Verbeke","year":"2015","unstructured":"Verbeke, L. et al. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats. Am. J. Pathol. 185, 409\u2013419 (2015).","journal-title":"Am. J. Pathol."},{"key":"376_CR91","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.jhep.2015.12.010","volume":"64","author":"M Ubeda","year":"2016","unstructured":"Ubeda, M. et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats. J. Hepatol. 64, 1049\u20131057 (2016).","journal-title":"J. Hepatol."},{"key":"376_CR92","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.jhep.2019.06.017","volume":"71","author":"M Sorribas","year":"2019","unstructured":"Sorribas, M. et al. FXR modulates the gut\u2013vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis. J. Hepatol. 71, 1126\u20131140 (2019).","journal-title":"J. Hepatol."},{"key":"376_CR93","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jhep.2012.12.011","volume":"58","author":"T Reiberger","year":"2013","unstructured":"Reiberger, T. et al. Non-selective \u03b2-blocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J. Hepatol. 58, 911\u2013921 (2013).","journal-title":"J. Hepatol."},{"key":"376_CR94","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/hep.510310109","volume":"31","author":"M Perez-Paramo","year":"2000","unstructured":"Perez-Paramo, M. et al. Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites. Hepatology 31, 43\u201348 (2000).","journal-title":"Hepatology"},{"key":"376_CR95","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/j.1478-3231.2009.02038.x","volume":"29","author":"M Senzolo","year":"2009","unstructured":"Senzolo, M. et al. \u03b2-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. Liver Int. 29, 1189\u20131193 (2009).","journal-title":"Liver Int."},{"key":"376_CR96","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1038\/ajg.2009.457","volume":"104","author":"M Senzolo","year":"2009","unstructured":"Senzolo, M. et al. Oral propranolol decreases intestinal permeability in patients with cirrhosis: another protective mechanism against bleeding? Am. J. Gastroenterol. 104, 3115\u20133116 (2009).","journal-title":"Am. J. Gastroenterol."},{"key":"376_CR97","doi-asserted-by":"publisher","unstructured":"Lang, S. et al. Intestinal virome signature associated with severity of nonalcoholic fatty liver disease. Gastroenterology https:\/\/doi.org\/10.1053\/j.gastro.2020.07.005 (2020).","DOI":"10.1053\/j.gastro.2020.07.005"},{"key":"376_CR98","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.cell.2018.02.044","volume":"172","author":"TSB Schmidt","year":"2018","unstructured":"Schmidt, T. S. B., Raes, J. & Bork, P. The human gut microbiome: from association to modulation. Cell 172, 1198\u20131215 (2018).","journal-title":"Cell"},{"key":"376_CR99","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1053\/he.2000.5852","volume":"31","author":"M Malinchoc","year":"2000","unstructured":"Malinchoc, M. et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31, 864\u2013871 (2000).","journal-title":"Hepatology"},{"key":"376_CR100","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/bjs.1800600817","volume":"60","author":"RN Pugh","year":"1973","unstructured":"Pugh, R. N., Murray-Lyon, I. M., Dawson, J. L., Pietroni, M. C. & Williams, R. Transection of the oesophagus for bleeding oesophageal varices. Br. J. Surg. 60, 646\u2013649 (1973).","journal-title":"Br. J. Surg."},{"key":"376_CR101","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.jhep.2014.11.012","volume":"62","author":"R Jalan","year":"2015","unstructured":"Jalan, R. et al. The CLIF consortium acute decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J. Hepatol. 62, 831\u2013840 (2015).","journal-title":"J. Hepatol."},{"key":"376_CR102","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1053\/jhep.2002.33715","volume":"36","author":"J Such","year":"2002","unstructured":"Such, J. et al. Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology 36, 135\u2013141 (2002).","journal-title":"Hepatology"},{"key":"376_CR103","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fimmu.2019.00069","volume":"10","author":"C Alvarez-Silva","year":"2019","unstructured":"Alvarez-Silva, C. et al. Compartmentalization of immune response and microbial translocation in decompensated cirrhosis. Front. Immunol. 10, 69 (2019).","journal-title":"Front. Immunol."},{"key":"376_CR104","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature11450","volume":"490","author":"J Qin","year":"2012","unstructured":"Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55\u201360 (2012).","journal-title":"Nature"},{"key":"376_CR105","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1136\/gutjnl-2015-309800","volume":"66","author":"J Yu","year":"2017","unstructured":"Yu, J. et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66, 70\u201378 (2017).","journal-title":"Gut"},{"key":"376_CR106","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/jgh.12932","volume":"30","author":"Y Chen","year":"2015","unstructured":"Chen, Y. et al. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality. J. Gastroenterol. Hepatol. 30, 1429\u20131437 (2015).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"376_CR107","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.cgh.2018.07.022","volume":"17","author":"JS Bajaj","year":"2019","unstructured":"Bajaj, J. S. et al. Association between intestinal microbiota collected at hospital admission and outcomes of patients with cirrhosis. Clin. Gastroenterol. Hepatol. 17, 756\u2013765.e3 (2019).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"376_CR108","volume":"8","author":"JS Bajaj","year":"2018","unstructured":"Bajaj, J. S. et al. Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis. JCI Insight 8, e98019 (2018).","journal-title":"JCI Insight"},{"key":"376_CR109","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/lt.24754","volume":"23","author":"JS Bajaj","year":"2017","unstructured":"Bajaj, J. S. et al. Liver transplant modulates gut microbial dysbiosis and cognitive function in cirrhosis. Liver Transpl. 23, 907\u2013914 (2017).","journal-title":"Liver Transpl."},{"key":"376_CR110","doi-asserted-by":"crossref","first-page":"G675","DOI":"10.1152\/ajpgi.00152.2012","volume":"303","author":"JS Bajaj","year":"2012","unstructured":"Bajaj, J. S. et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G675\u2013G685 (2012).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"376_CR111","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/hep.27819","volume":"62","author":"JS Bajaj","year":"2015","unstructured":"Bajaj, J. S. et al. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology 62, 1260\u20131271 (2015).","journal-title":"Hepatology"},{"key":"376_CR112","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-01973-8","volume":"8","author":"C Duvallet","year":"2017","unstructured":"Duvallet, C., Gibbons, S. M., Gurry, T., Irizarry, R. A. & Alm, E. J. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat. Commun. 8, 1784 (2017).","journal-title":"Nat. Commun."},{"key":"376_CR113","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41591-019-0406-6","volume":"25","author":"J Wirbel","year":"2019","unstructured":"Wirbel, J. et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat. Med. 25, 679\u2013689 (2019).","journal-title":"Nat. Med."},{"key":"376_CR114","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41591-019-0405-7","volume":"25","author":"AM Thomas","year":"2019","unstructured":"Thomas, A. M. et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat. Med. 25, 667\u2013678 (2019).","journal-title":"Nat. Med."},{"key":"376_CR115","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nmeth.4468","volume":"14","author":"E Pasolli","year":"2017","unstructured":"Pasolli, E. et al. Accessible, curated metagenomic data through ExperimentHub. Nat. Methods 14, 1023\u20131024 (2017).","journal-title":"Nat. Methods"},{"key":"376_CR116","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nature25979","volume":"555","author":"L Maier","year":"2018","unstructured":"Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623\u2013628 (2018).","journal-title":"Nature"},{"key":"376_CR117","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/hep.28737","volume":"64","author":"G Dam","year":"2016","unstructured":"Dam, G., Vilstrup, H., Watson, H. & Jepsen, P. Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology 64, 1265\u20131272 (2016).","journal-title":"Hepatology"},{"key":"376_CR118","volume":"8","author":"C Llorente","year":"2017","unstructured":"Llorente, C. et al. Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus. Nat. Commun. 8, 837 (2017).","journal-title":"Nat. Commun."},{"key":"376_CR119","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1038\/nature14851","volume":"525","author":"JS Bajaj","year":"2015","unstructured":"Bajaj, J. S., Betrapally, N. S. & Gillevet, P. M. Decompensated cirrhosis and microbiome interpretation. Nature 525, E1\u2013E2 (2015).","journal-title":"Nature"},{"key":"376_CR120","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/j.1872-034X.2012.01015.x","volume":"42","author":"K Holte","year":"2012","unstructured":"Holte, K., Krag, A. & Gluud, L. L. Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy. Hepatol. Res. 42, 1008\u20131015 (2012).","journal-title":"Hepatol. Res."},{"key":"376_CR121","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1053\/j.gastro.2014.08.031","volume":"147","author":"RK Dhiman","year":"2014","unstructured":"Dhiman, R. K. et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 147, 1327\u20131337.e3 (2014).","journal-title":"Gastroenterology"},{"key":"376_CR122","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/hep.29791","volume":"68","author":"JS Bajaj","year":"2018","unstructured":"Bajaj, J. S. et al. Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort. Hepatology 68, 234\u2013247 (2018).","journal-title":"Hepatology"},{"key":"376_CR123","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/apt.13436","volume":"43","author":"RB Sartor","year":"2016","unstructured":"Sartor, R. B. Review article: the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases. Aliment. Pharmacol. Ther. 43, 27\u201336 (2016).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"376_CR124","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.cgh.2012.02.025","volume":"10","author":"GN Kalambokis","year":"2012","unstructured":"Kalambokis, G. N. et al. Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites. Clin. Gastroenterol. Hepatol. 10, 815\u2013818 (2012).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"376_CR125","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jgh.12070","volume":"28","author":"J Vlachogiannakos","year":"2013","unstructured":"Vlachogiannakos, J. et al. Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis. J. Gastroenterol. Hepatol. 28, 450\u2013455 (2013).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"376_CR126","volume":"9","author":"P Lutz","year":"2014","unstructured":"Lutz, P. et al. Impact of rifaximin on the frequency and characteristics of spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites. PLoS ONE 9, e93909 (2014).","journal-title":"PLoS ONE"},{"key":"376_CR127","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/hep.28898","volume":"65","author":"N Kimer","year":"2017","unstructured":"Kimer, N. et al. Rifaximin has no effect on hemodynamics in decompensated cirrhosis: a randomized, double-blind, placebo-controlled trial. Hepatology 65, 592\u2013603 (2017).","journal-title":"Hepatology"},{"key":"376_CR128","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/jgh.13852","volume":"33","author":"N Kimer","year":"2018","unstructured":"Kimer, N. et al. Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis; a randomized trial. J. Gastroenterol. Hepatol. 33, 307\u2013314 (2018).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"376_CR129","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1053\/j.gastro.2016.01.004","volume":"150","author":"JG Abraldes","year":"2016","unstructured":"Abraldes, J. G. et al. Addition of simvastatin to standard therapy for the prevention of variceal rebleeding does not reduce rebleeding but increases survival in patients with cirrhosis. Gastroenterology 150, 1160\u20131170.e3 (2016).","journal-title":"Gastroenterology"},{"key":"376_CR130","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1053\/j.gastro.2009.01.043","volume":"136","author":"JG Abraldes","year":"2009","unstructured":"Abraldes, J. G. et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology 136, 1651\u20131658 (2009).","journal-title":"Gastroenterology"},{"key":"376_CR131","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1053\/j.gastro.2018.07.022","volume":"155","author":"DM Tripathi","year":"2018","unstructured":"Tripathi, D. M. et al. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension. Gastroenterology 155, 1564\u20131577 (2018).","journal-title":"Gastroenterology"},{"key":"376_CR132","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41586-020-2269-x","volume":"581","author":"S Vieira-Silva","year":"2020","unstructured":"Vieira-Silva, S. et al. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature 581, 310\u2013315 (2020).","journal-title":"Nature"},{"key":"376_CR133","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S2468-1253(19)30320-6","volume":"5","author":"E Pose","year":"2020","unstructured":"Pose, E. et al. Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol. Hepatol. 5, 31\u201341 (2020).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"376_CR134","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jhep.2018.03.024","volume":"69","author":"European Association for the Study of the Liver","year":"2018","unstructured":"European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J. Hepatol. 69, 406\u2013460 (2018).","journal-title":"J. Hepatol."},{"key":"376_CR135","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/gutjnl-2011-300779","volume":"61","author":"R Wiest","year":"2012","unstructured":"Wiest, R., Krag, A. & Gerbes, A. Spontaneous bacterial peritonitis: recent guidelines and beyond. Gut 61, 297\u2013310 (2012).","journal-title":"Gut"},{"key":"376_CR136","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1053\/j.gastro.2018.08.026","volume":"155","author":"R Moreau","year":"2018","unstructured":"Moreau, R. et al. Effects of long-term norfloxacin therapy in patients with advanced cirrhosis. Gastroenterology 155, 1816\u20131827.e9 (2018).","journal-title":"Gastroenterology"},{"key":"376_CR137","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1002\/hep.28330","volume":"63","author":"J Fernandez","year":"2016","unstructured":"Fernandez, J., Tandon, P., Mensa, J. & Garcia-Tsao, G. Antibiotic prophylaxis in cirrhosis: good and bad. Hepatology 63, 2019\u20132031 (2016).","journal-title":"Hepatology"},{"key":"376_CR138","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.jhep.2018.10.027","volume":"70","author":"J Fernandez","year":"2019","unstructured":"Fernandez, J. et al. Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe. J. Hepatol. 70, 398\u2013411 (2019).","journal-title":"J. Hepatol."},{"key":"376_CR139","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1053\/j.gastro.2018.12.005","volume":"156","author":"S Piano","year":"2019","unstructured":"Piano, S. et al. Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide. Gastroenterology 156, 1368\u20131380.e10 (2019).","journal-title":"Gastroenterology"},{"key":"376_CR140","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nrendo.2014.210","volume":"11","author":"LM Cox","year":"2015","unstructured":"Cox, L. M. & Blaser, M. J. Antibiotics in early life and obesity. Nat. Rev. Endocrinol. 11, 182\u2013190 (2015).","journal-title":"Nat. Rev. Endocrinol."},{"key":"376_CR141","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1172\/JCI105694","volume":"46","author":"RM Kerr","year":"1967","unstructured":"Kerr, R. M., Du Bois, J. J. & Holt, P. R. Use of 125-I- and 51-Cr-labeled albumin for the measurement of gastrointestinal and total albumin catabolism. J. Clin. Invest. 46, 2064\u20132082 (1967).","journal-title":"J. Clin. Invest."},{"key":"376_CR142","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fphys.2015.00359","volume":"6","author":"J Gortzen","year":"2015","unstructured":"Gortzen, J. et al. Interplay of matrix stiffness and c-SRC in hepatic fibrosis. Front. Physiol. 6, 359 (2015).","journal-title":"Front. Physiol."},{"key":"376_CR143","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/MEG.0b013e3280101f7d","volume":"19","author":"S Klammt","year":"2007","unstructured":"Klammt, S. et al. Albumin-binding function is reduced in patients with decompensated cirrhosis and correlates inversely with severity of liver disease assessed by model for end-stage liver disease. Eur. J. Gastroenterol. Hepatol. 19, 257\u2013263 (2007).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"376_CR144","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/hep.22913","volume":"50","author":"R Jalan","year":"2009","unstructured":"Jalan, R. et al. Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality. Hepatology 50, 555\u2013564 (2009).","journal-title":"Hepatology"},{"key":"376_CR145","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1002\/hep.27322","volume":"60","author":"M Domenicali","year":"2014","unstructured":"Domenicali, M. et al. Posttranscriptional changes of serum albumin: clinical and prognostic significance in hospitalized patients with cirrhosis. Hepatology 60, 1851\u20131860 (2014).","journal-title":"Hepatology"},{"key":"376_CR146","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.jceh.2014.08.007","volume":"4","author":"M Bernardi","year":"2014","unstructured":"Bernardi, M., Ricci, C. S. & Zaccherini, G. Role of human albumin in the management of complications of liver cirrhosis. J. Clin. Exp. Hepatol. 4, 302\u2013311 (2014).","journal-title":"J. Clin. Exp. Hepatol."},{"key":"376_CR147","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nm.3516","volume":"20","author":"AJ O\u2019Brien","year":"2014","unstructured":"O\u2019Brien, A. J. et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat. Med. 20, 518\u2013523 (2014).","journal-title":"Nat. Med."},{"key":"376_CR148","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.cgh.2019.07.055","volume":"18","author":"J Fernandez","year":"2020","unstructured":"Fernandez, J. et al. Efficacy of albumin treatment for patients with cirrhosis and infections unrelated to spontaneous bacterial peritonitis. Clin. Gastroenterol. Hepatol. 18, 963\u2013973.e14 (2020).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"376_CR149","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1053\/j.gastro.2019.03.021","volume":"157","author":"J Fernandez","year":"2019","unstructured":"Fernandez, J. et al. Effects of albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis. Gastroenterology 157, 149\u2013162 (2019).","journal-title":"Gastroenterology"},{"key":"376_CR150","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/S0140-6736(18)30840-7","volume":"391","author":"P Caraceni","year":"2018","unstructured":"Caraceni, P. et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet 391, 2417\u20132429 (2018).","journal-title":"Lancet"},{"key":"376_CR151","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.jhep.2012.06.013","volume":"57","author":"M Guevara","year":"2012","unstructured":"Guevara, M. et al. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J. Hepatol. 57, 759\u2013765 (2012).","journal-title":"J. Hepatol."},{"key":"376_CR152","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.jhep.2014.11.017","volume":"62","author":"T Thevenot","year":"2015","unstructured":"Thevenot, T. et al. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J. Hepatol. 62, 822\u2013830 (2015).","journal-title":"J. Hepatol."},{"key":"376_CR153","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1136\/gutjnl-2019-318843","volume":"69","author":"M Bernardi","year":"2020","unstructured":"Bernardi, M. et al. Albumin in decompensated cirrhosis: new concepts and perspectives. Gut 69, 1127\u20131138 (2020).","journal-title":"Gut"},{"key":"376_CR154","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.cmet.2017.04.001","volume":"25","author":"R Loomba","year":"2017","unstructured":"Loomba, R. et al. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab. 25, 1054\u20131062.e5 (2017).","journal-title":"Cell Metab."},{"key":"376_CR155","doi-asserted-by":"crossref","first-page":"G824","DOI":"10.1152\/ajpgi.00230.2018","volume":"315","author":"JS Bajaj","year":"2018","unstructured":"Bajaj, J. S. et al. Periodontal therapy favorably modulates the oral\u2013gut\u2013hepatic axis in cirrhosis. Am. J. Physiol. Gastrointest. Liver Physiol. 315, G824\u2013G837 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"376_CR156","first-page":"301","volume":"304","author":"Y Braham","year":"1987","unstructured":"Braham, Y., Meunier, G. & Meunier, B. [Demonstration of an oxidative biotransformation of 9-methoxyellipticine. Comparison with the case of 9-hydroxyellipticine] [French]. C. R. Acad. Sci. III 304, 301\u2013306 (1987).","journal-title":"C. R. Acad. Sci. III"},{"key":"376_CR157","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/hep.29306","volume":"66","author":"JS Bajaj","year":"2017","unstructured":"Bajaj, J. S. et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology 66, 1727\u20131738 (2017).","journal-title":"Hepatology"},{"key":"376_CR158","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1053\/j.gastro.2019.01.033","volume":"156","author":"JS Bajaj","year":"2019","unstructured":"Bajaj, J. S. et al. Long-term outcomes of fecal microbiota transplantation in patients with cirrhosis. Gastroenterology 156, 1921\u20131923.e3 (2019).","journal-title":"Gastroenterology"},{"key":"376_CR159","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1002\/hep.30690","volume":"70","author":"JS Bajaj","year":"2019","unstructured":"Bajaj, J. S. et al. Fecal microbial transplant capsules are safe in hepatic encephalopathy: a phase 1, randomized, placebo-controlled trial. Hepatology 70, 1690\u20131703 (2019).","journal-title":"Hepatology"},{"key":"376_CR160","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.133410","volume":"4","author":"JS Bajaj","year":"2019","unstructured":"Bajaj, J. S. et al. Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis. JCI Insight 4, e133410 (2019).","journal-title":"JCI Insight"},{"key":"376_CR161","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1056\/NEJMoa1910437","volume":"381","author":"Z DeFilipp","year":"2019","unstructured":"DeFilipp, Z. et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N. Engl. J. Med. 381, 2043\u20132050 (2019).","journal-title":"N. Engl. J. Med."},{"key":"376_CR162","doi-asserted-by":"crossref","first-page":"G563","DOI":"10.1152\/ajpgi.00370.2018","volume":"316","author":"P Hartmann","year":"2019","unstructured":"Hartmann, P., Chu, H., Duan, Y. & Schnabl, B. Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either. Am. J. Physiol. Gastrointest. Liver Physiol. 316, G563\u2013G573 (2019).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"376_CR163","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1002\/hep.23710","volume":"51","author":"AK Burroughs","year":"2010","unstructured":"Burroughs, A. K. & Thalheimer, U. Hepatic venous pressure gradient in 2010: optimal measurement is key. Hepatology 51, 1894\u20131896 (2010).","journal-title":"Hepatology"},{"key":"376_CR164","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1053\/j.gastro.2007.05.024","volume":"133","author":"C Ripoll","year":"2007","unstructured":"Ripoll, C. et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 133, 481\u2013488 (2007).","journal-title":"Gastroenterology"},{"key":"376_CR165","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1159\/000490262","volume":"34","author":"J Trebicka","year":"2018","unstructured":"Trebicka, J., Reiberger, T. & Laleman, W. Gut\u2013liver axis links portal hypertension to acute-on-chronic liver failure. Visc. Med. 34, 270\u2013275 (2018).","journal-title":"Visc. Med."},{"key":"376_CR166","volume":"9","author":"EJ Cho","year":"2019","unstructured":"Cho, E. J. et al. Circulating microbiota-based metagenomic signature for detection of hepatocellular carcinoma. Sci. Rep. 9, 7536 (2019).","journal-title":"Sci. Rep."},{"key":"376_CR167","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1136\/gutjnl-2017-315084","volume":"68","author":"Z Ren","year":"2019","unstructured":"Ren, Z. et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut 68, 1014\u20131023 (2019).","journal-title":"Gut"},{"key":"376_CR168","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1056\/NEJMoa0907893","volume":"362","author":"NM Bass","year":"2010","unstructured":"Bass, N. M. et al. Rifaximin treatment in hepatic encephalopathy. N. Engl. J. Med. 362, 1071\u20131081 (2010).","journal-title":"N. Engl. J. Med."},{"key":"376_CR169","doi-asserted-by":"crossref","unstructured":"Arroyo, V., Claria, J. & Trebicka, J. in Encyclopedia of Gastroenterology 2nd edn (ed. Gerbes, A. L.) 436\u2013443 (Elsevier, 2020).","DOI":"10.1016\/B978-0-12-801238-3.65780-X"}],"container-title":["Nature Reviews Gastroenterology &amp; Hepatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41575-020-00376-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41575-020-00376-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41575-020-00376-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:52:20Z","timestamp":1684619540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41575-020-00376-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":169,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["376"],"URL":"https:\/\/doi.org\/10.1038\/s41575-020-00376-3","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]},"assertion":[{"value":"7 October 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}