{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:56:37Z","timestamp":1790200597360,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007210","name":"RWTH Aachen University","doi-asserted-by":"publisher","award":["IZKF #O3-6"],"award-info":[{"award-number":["IZKF #O3-6"]}],"id":[{"id":"10.13039\/501100007210","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007210","name":"RWTH Aachen University","doi-asserted-by":"publisher","award":["START program #120\/17"],"award-info":[{"award-number":["START program #120\/17"]}],"id":[{"id":"10.13039\/501100007210","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC1382 project A08 #403224013"],"award-info":[{"award-number":["CRC1382 project A08 #403224013"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC1382 project Q02 #403224013"],"award-info":[{"award-number":["CRC1382 project Q02 #403224013"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>A considerable percentage of the population is affected by alcoholic liver disease (ALD). It is characterized by inflammatory signals from the liver and other organs, such as the intestine. The NLR family pyrin domain containing 6 (NLRP6) inflammasome complex is one of the most important inflammatory mediators. The aim of this study was to evaluate a novel mouse model for ALD characterized by 8-week chronic-plus-binge ethanol administration and to investigate the role of NLRP6 inflammasome for intestinal homeostasis and ALD progression using Nlrp6-\/- mice. We showed that chronic-plus-binge ethanol administration triggers hepatic steatosis, injury, and neutrophil infiltration. Furthermore, we discovered significant changes of intestinal microbial communities, including increased relative abundances of bacteria within the phyla Bacteroidota and Campilobacterota, as well as reduced Firmicutes. In this ALD model, inhibiting NLRP6 signaling had no effect on liver steatosis or damage, but had a minor impact on intestinal homeostasis via affecting intestinal epithelium function and gut microbiota. Surprisingly, Nlrp6 loss resulted in significantly decreased hepatic immune cell infiltration. As a result, our novel mouse model encompasses several aspects of human ALD, such as intestinal dysbiosis. Interfering with NLRP6 inflammasome activity reduced hepatic immune cell recruitment, indicating a disease-aggravating role of NLRP6 during ALD.<\/jats:p>","DOI":"10.3390\/cells11020182","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T03:41:32Z","timestamp":1641440492000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["NLRP6 Inflammasome Modulates Disease Progression in a Chronic-Plus-Binge Mouse Model of Alcoholic Liver Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Rebecca Elena","family":"Mainz","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-0085","authenticated-orcid":false,"given":"Stefanie","family":"Albers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6680-5181","authenticated-orcid":false,"given":"Roland","family":"Sonntag","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Simone","family":"Treichel","sequence":"additional","affiliation":[{"name":"Functional Microbiome Research Group, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Clavel","sequence":"additional","affiliation":[{"name":"Functional Microbiome Research Group, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eicke","family":"Latz","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0047-3794","authenticated-orcid":false,"given":"Kai Markus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-3055","authenticated-orcid":false,"given":"Tobias","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1055\/s-2004-832936","article-title":"Epidemiology of alcoholic liver disease","volume":"24","author":"Mandayam","year":"2004","journal-title":"Semin. 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