A team of scientists found a promising treatment for alcoholic liver disease by targeting gut bacteria in a different way than antibiotics, phage therapy. In a Nature study paper, the team describes how they used bacteriophage, a virus that infects bacteria, to successfully eliminate alcoholic liver disease in mice.
Enterococcus faecalis is a gut bacterium that releases a toxin that kills liver cells. The scientists used a particular mixture of phages to eliminate E. faecalis selectively. Individuals with alcoholic liver disease have more E. faecalis in their guts than those who don’t have this condition. Levels of this bacterium in the gut microbiome are found to correlate with the severity of the disease.
Bernd Schnabl, senior study author, said:
We not only linked a specific bacterial toxin to worse clinical outcomes in people with alcoholic liver disease, we found a way to break that link by precisely editing gut microbiota with phages.
Alcoholic Liver Disease
Alcoholic liver disease is the #1 cause of death in people with liver conditions. People get this disease when their liver is damaged from drinking too much alcohol. The disease can range from mild to life-threatening dependent upon how much alcohol a person drinks and other health factors unique to the individual.
The first stage of alcoholic liver disease, which can develop after just a few days of heavy alcohol use, is a fatty liver. After over ten years of heavy drinking, alcohol-related fatty liver evolves to fibrosis, and then to cirrhosis. In some cases, the disease takes on a very severe form called alcoholic hepatitis.
In 2017, the Centers for Disease Control and Prevention (CDC) found Alcoholic hepatitis and other severe forms of alcoholic liver disease responsible for about 22,246 deaths in the U.S.
The standard medication for alcoholic hepatitis is corticosteroids. However, these drugs are not very effective, and most of the people die within three months of receiving a diagnosis. Currently, the only cure is to have a liver transplant, but livers are not readily available and have a very long waiting list.
The Study
While scientists were investigating the cause of injury and cell death in the liver, they discovered it was because of the cytolysin, which is a toxin that E. faecalis produces. After samples from people with alcoholic hepatitis were analyzed, it was found that the majority of people who tested positive for cytolysin ended up dying within 180 days of being admitted to the hospital. Meanwhile, to those who tested negative for cytolysin, only a small minority died within 180 days.
Isolating four bacteriophages that target cytolysin-secreting E. faecalis bacteria, the team was ready to attempt the treatment of alcoholic-induced liver disease in mice. When treating mice with these phages they eliminated the disease and found no other strains of bacteria were affected.
Phage Therapy Treatment
The approach of using viruses to eradicate systemic bacterial infections is called phage therapy. Scientists began experimenting with phage therapy 100 years ago, however, the advent of antibiotics reduced interest. Researchers are beginning to gain insight into this method of treatment and perform further study on utilizing phages as a treatment for bacteria-related illnesses.
Prof. Debbie L. Shawcross, study co-author, said:
This novel avenue of research now needs to be expanded to test the safety and effectiveness of phage therapy in human clinical trials in people with alcohol-related disease.
At the moment, phage therapy is not ready to be offered as a treatment for alcoholic liver disease, but when it is ready, it will be excellent news to anyone who has this condition.
