Scientists find out why alcoholic liver is so deadly

viruses, known as phages, can infect a toxic gut bacteria that makes alcoholic liver disease more serious. Photo Source: BERND SCHNABL LAB
For severe alcoholics with alcohol-damaged livers, an organ transplant is often the only realistic option. But because of the lack of a supply liver and regulations prohibiting transplants for people who have not yet given up drinking, many end up waiting to die.
the United States, thousands of people die each year from alcoholic liver disease, and some people get sick much faster than others. Now, scientists have found the cause of this difference -- a toxin produced by certain strains of common gut bacteria.
researchers also tested a potential treatment in mice based on a virus found in sewers that could kill bacteria.
Jasmohan Bajaj, a gastroenterologist and liver specialist at Virginia Commonwealth University in Richmond, asked why some alcoholics with liver disease are in a much worse situation than others. "It's always been a puzzle."
, a gastroenterologist at the University of California, San Diego (UCSD), and his colleagues believe fecal enterococci provides an explanation. In stool samples from patients with alcoholic liver disease, the amount of fecal enterococcal was 2,700 times higher than in people who did not drink alcohol, although the amount of bacteria was not directly related to the patient's final outcome. Instead, the researchers found that a cell-destroying toxin produced by a specific fecal enterococcal strain called cytolysin may be the cause of severe symptoms in some patients with alcoholic liver disease.
Schnabl and colleagues report the findings this week in the journal Nature.
less than 5 percent of healthy people carry strains that produce toxins, but the researchers found that 30 percent of the hospitalized patients they tested for alcoholic liver disease carried the strain. The mortality rate for these alcoholic liver disease patients was much higher within 180 days of treatment - 89 per cent of cytolysis-positive patients died, while other patients had a mortality rate of only 3.8 per cent.
is actually a key factor in mortality and the severity of liver disease," schnabl said. "
Schnabl and colleagues don't know why people with alcoholic liver disease multiply the strain in large numbers. But the team finally confirmed the deadly effects of the bacteria by implanting toxin-producing fecal enterococcus in some mice, as well as non-toxic strains in others, and then pouring alcohol into the rodents to damage their livers. Mice carrying toxin-producing bacteria were much worse off than the control group.
, the team found a way to precisely remove the toxic fecal enterococcal bacteria and looked at whether the rodents' symptoms had improved.
the widespread lethality of traditional antibiotics, the team recruited colleagues from UCSD who study the use of phages or viruses. These viruses kill specific bacteria and have been used by researchers (many in Russia and Eastern Europe) for decades to treat diseases such as dysentery and gangrene.
at the university's sewage treatment plant, a ready-made "buffet" for fecal bacteria-eating organisms, the team found phages that target fecal enterococcus, which dissolves cells. When mice carrying the deadly bacteria were treated with the phage, they had less liver damage, less inflammation, and less cell solubility in the liver than the control group.
can reduce the incidence of alcoholic liver disease, but we can't fully restore mice with alcoholic liver disease to baseline levels," Schnabl said.
Bajaj called the study of mice "very detailed," adding that while phage therapy is far from ready for clinical use, it is pushing the study of alcoholic liver disease in "an encouraging direction."
UCSD's research team is currently working to build a library of phages isolated from patients with different liver diseases that can effectively fight fecal enterococcal cell dissolved positive strains. The researchers plan to assess the safety of phages and then consider testing them in patients with severe conditions.
Gorski, a phage expert at the Polish Academy of Sciences, agreed with the plan. "Now is a good time to conduct clinical trials of phages, " he said. (Source: Zhao Xixi, China Science Journal)
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