|  Help  |  About  |  Contact Us

Publication : Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

First Author  Duan Y Year  2019
Journal  Nature Volume  575
Issue  7783 Pages  505-511
PubMed ID  31723265 Mgi Jnum  J:286892
Mgi Id  MGI:6407565 Doi  10.1038/s41586-019-1742-x
Citation  Duan Y, et al. (2019) Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 575(7783):505-511
abstractText  Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality(1-3). Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice(4), but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis(5,6)-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
Paste the following link
Quick Links:
SummaryExpressionOther
 
Quick Links:
SummaryExpressionOther
 
Lists
This Publication isn't in any lists. Upload a list.

Expression

Publication --> Expression annotations

 

Other

46 Authors

3 Bio Entities

Trail: Publication

0 Expression





MouseMine is a collaboration between MGI at The Jackson Laboratory and the InterMine project at the Cambridge Systems Biology Centre. MouseMine is funded through a grant from the NIH/NHGRI.The Jackson Laboratory makes no representation about the suitability or accuracy of this software or data for any purpose, and makes no warranties, either express or implied, including merchantability and fitness for a particular purpose or that the use of this software or data will not infringe any third party patents, copyrights, trademarks, or other rights. the software and data are provided "as is". This software and data are provided to enhance knowledge and encourage progress in the scientific community and are to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of the Jackson Laboratory.

Copyright © 2017 by The Jackson Laboratory. All Rights Reserved

© 2002 - 2017 Department of Genetics, University of Cambridge, Downing Street,
Cambridge CB2 3EH, United Kingdom