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Immunol."],"abstract":"<jats:p>Diverse liver diseases undergo a similar pathophysiological process in which liver regeneration follows a liver injury. Given the important role of the gut-liver axis in health and diseases, the role of gut microbiota-derived signals in liver injury and regeneration has attracted much attention. It has been observed that the composition of gut microbiota dynamically changes in the process of liver regeneration after partial hepatectomy, and gut microbiota modulation by antibiotics or probiotics affects both liver injury and regeneration. Mechanically, through the portal vein, the liver is constantly exposed to gut microbial components and metabolites, which have immense effects on the immunity and metabolism of the host. Emerging data demonstrate that gut-derived lipopolysaccharide, gut microbiota-associated bile acids, and other bacterial metabolites, such as short-chain fatty acids and tryptophan metabolites, may play multifaceted roles in liver injury and regeneration. In this perspective, we provide an overview of the possible molecular mechanisms by which gut microbiota-derived signals modulate liver injury and regeneration, highlighting the potential roles of gut microbiota in the development of gut microbiota-based therapies to alleviate liver injury and promote liver regeneration.<\/jats:p>","DOI":"10.3389\/fimmu.2021.775526","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T04:10:32Z","timestamp":1639109432000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":165,"title":["The Gut-Liver Axis in Health and Disease: The Role of Gut Microbiota-Derived Signals in Liver Injury and Regeneration"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhipeng","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28988","article-title":"Hepatostat: Liver Regeneration and Normal Liver Tissue Maintenance","volume":"65","author":"Michalopoulos","year":"2017","journal-title":"Hepatology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.08.004","article-title":"Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease","volume":"149","author":"Michalopoulos","year":"2015","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.97","article-title":"Liver Regeneration - Mechanisms and Models to Clinical Application","volume":"13","author":"Forbes","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20969","article-title":"Liver Regeneration","volume":"43","author":"Fausto","year":"2006","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/term.3009","article-title":"The Role of Microbiota in Tissue Repair and Regeneration","volume":"14","author":"Shavandi","year":"2020","journal-title":"J Tissue Eng Regener Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1985.249.5.R551","article-title":"Gut-Derived Endotoxin Elicits Hepatotrophic Factor Secretion for Liver Regeneration","volume":"249","author":"Cornell","year":"1985","journal-title":"Am J Physiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1985.249.5.R563","article-title":"Restriction of Gut-Derived Endotoxin Impairs DNA Synthesis for Liver Regeneration","volume":"249","author":"Cornell","year":"1985","journal-title":"Am J Physiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840110603","article-title":"Depressed Liver Regeneration After Partial Hepatectomy of Germ-Free, Athymic and Lipopolysaccharide-Resistant Mice","volume":"11","author":"Cornell","year":"1990","journal-title":"Hepatology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043559","article-title":"Microbial Contribution to the Human Metabolome: Implications for Health and Disease","volume":"24","author":"Van Treuren","year":"2019","journal-title":"Annu Rev Pathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0252-2","article-title":"Immune Recognition of Microbial Metabolites","volume":"20","author":"Garrett","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.01.017","article-title":"Microbiota Changes and Intestinal Microbiota Transplantation in Liver Diseases and Cirrhosis","volume":"72","author":"Bajaj","year":"2020","journal-title":"J Hepatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.700058","article-title":"Role of the Gut Microbiota in Regulating Non-Alcoholic Fatty Liver Disease in Children and Adolescents","volume":"8","author":"Tokuhara","year":"2021","journal-title":"Front Nutr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s00248-010-9801-8","article-title":"Intestinal Microbiota was Assessed in Cirrhotic Patients With Hepatitis B Virus Infection. 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