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The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression

by Dishen Chen 1,†, Thanh H. Le 1,2,†, Haleh Shahidipour 1,3, Scott A. Read 1,3,*,† and Golo Ahlenstiel 1,3,4,*,†
1
Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia
2
School of Medicine, Western Sydney University, Campbelltown 2560, NSW, Australia
3
Blacktown Medical School, Western Sydney University, Blacktown 2148, NSW, Australia
4
Blacktown Hospital, Blacktown 2148, NSW, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(11), 1324; https://doi.org/10.3390/cells8111324
Received: 30 September 2019 / Revised: 22 October 2019 / Accepted: 23 October 2019 / Published: 27 October 2019
Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis. View Full-Text
Keywords: fibrosis; cirrhosis; alcoholic liver disease; NAFLD; NASH; intestinal permeability; bacterial translocation; innate immunity fibrosis; cirrhosis; alcoholic liver disease; NAFLD; NASH; intestinal permeability; bacterial translocation; innate immunity
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Chen, D.; Le, T.H.; Shahidipour, H.; Read, S.A.; Ahlenstiel, G. The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression. Cells 2019, 8, 1324.

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