Researchers at University of California San Diego School of Medicine and their collaborators have now for the first time successfully applied phage therapy in mice for a condition that's not considered a classic bacterial infection: alcoholic liver disease.
The study publishes November 13, 2019 in Nature.
Toxin - Outcomes - Patients - Liver - Disease
"We not only linked a specific bacterial toxin to worse clinical outcomes in patients with alcoholic liver disease, we found a way to break that link by precisely editing gut microbiota with phages," said senior author Bernd Schnabl, MD, professor of medicine and gastroenterology at UC San Diego School of Medicine and director of the National Institutes of Health-funded San Diego Digestive Diseases Research Center.
Up to 75 percent of patients with severe alcoholic hepatitis, the most serious form of alcohol-related liver disease, die within 90 days of diagnosis. The condition is most commonly treated with corticosteroids, but they aren't highly effective. Early liver transplantation is the only cure, but is only offered at select medical centers to a limited number of patients. In fact, there are only approximately 8,000 liver transplants for all reasons in the United States each year, according to the American Liver Foundation, with a waiting list of roughly 14,000 people.
Alcohol - Liver - Cells - Bernd - Team
Alcohol itself can directly damage liver cells. But Bernd and team had previously discovered that alcohol is also harmful to the liver for a second reason: It diminishes natural gut antibiotics, leaving mice more prone to bacterial growth in the liver and exacerbating alcohol-induced liver disease.
In the current study, Bernd's team -- including many collaborators around the world -- addressed two primary questions: How do gut bacteria contribute to liver damage? And can phages be used to reduce the bacteria and thus alleviate alcoholic liver disease?
Researchers - Liver - Cells - Cytolysin - Toxin
The researchers discovered that liver cells are injured by cytolysin, a toxin secreted by Enterococcus faecalis, a type...
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