Today, the top academic journal Nature published a study by the University of California, San Diego online. In this paper, scientists found that the toxin produced by an intestinal flora is closely related to the severity of alcoholic hepatitis, and the treatment of this intestinal flora can alleviate the liver injury of mouse model. The researchers pointed out that this not only brought reliable biomarkers, but also opened up potential new treatment ideas.
▲ The first authors of this study are Dr. Duan Yi, Dr. Christina llorente and correspondent Professor Bernd Schnabl.
We all know that drinking is harmful to the liver. In some extreme cases, the patient's condition will develop into severe alcoholic hepatitis. How serious is this situation? Statistics show that once the disease enters this stage, as many as 75% patients will die within 90 days. There is no particularly good treatment for this disease except early liver transplantation.
In a study on 20 16, the research group revealed the double harm of "drinking alcohol to damage the liver": on the one hand, alcohol can directly damage liver cells; On the other hand, alcohol will disturb the balance of intestinal flora, make some bacteria grow more easily in the liver, and further aggravate alcoholic liver disease.
▲ Alcohol can make some intestinal flora run to the liver to grow.
After this discovery, the researchers raised two key questions: first, which bacteria are involved in the deterioration of the disease? Second, how to control it?
In order to answer the first question, the researchers used 16S rRNA sequencing method to find the specific intestinal flora of patients with long-term alcoholism and alcoholic hepatitis. Sure enough, compared with the healthy control group, the composition of fecal flora of patients has changed obviously, and one kind of bacteria called enterococcus is particularly interesting. This kind of bacteria accounts for 5.59% in patients' feces. On the contrary, such bacteria can hardly be found in the feces of healthy people.
After careful excavation, the researchers further found that Enterococcus faecalis is the key to this difference. In patients with alcoholic hepatitis, the level of this bacteria is more than 2700 times that of the control group! Moreover, the higher the level of this bacteria, the more serious the patient's condition, which has obvious correlation.
▲ Whether there is cytolysin has a great influence on the survival of patients.
Why is this bacterium involved in the deterioration of the disease? The researchers speculate that this may be related to a bacterial exotoxin called "cytolysin". The observation of patient data supports the view that nearly 90% of patients who can detect cytolysin in the body will die within 180 days after admission. The mortality rate of patients without cytolysin is only 4%.
Mouse experiments also show that cytolysin is the key to the deterioration of liver disease. In the study, scientists implanted two kinds of Enterococcus faecalis into mice, one of which produced cytolysin and the other did not produce this toxin. The results showed that under the alcoholic diet, no matter what kind of Enterococcus faecalis can be found in the liver of mice, and the liver injury of the former is indeed more serious and the mortality rate is higher.
Here, we see a comprehensive model of liver injury caused by drinking-under the action of alcohol, some intestinal flora will "escape" to the liver. When these microorganisms secrete cytolysin, in addition to alcohol, they will also bring additional damage to the liver.
So now that we know the culprit, is there any way to bring them to justice? Because this is a specific microorganism, broad-spectrum antibiotics will definitely not work. At this point, the researchers turned their attention to "phage". As the name implies, this is a virus that can kill bacteria. And we have found that it is highly specific-usually, a phage will only kill one or several bacteria and will not affect other bacteria.
▲ Phage can be used to attack specific bacteria.
After screening, they found four kinds of bacteriophages, which can specifically target enterococcus faecalis secreting cytolysin. The results of the mouse experiment are very exciting-these bacteria have been eliminated and the liver symptoms of mice have been alleviated. However, the researchers also pointed out that this is still the result of mouse experiments. In order to test whether it is safe and effective in human body, we need to conduct a larger clinical trial.
In a word, "we not only linked a specific bacterial toxin to the poor prognosis of patients, but also found a way to cut off this connection accurately through phage," said Professor Bernd Schnabl, the correspondent of this study. "Based on these findings, we believe that detecting the cytolysin gene in the feces of patients with alcoholic hepatitis will be a very good biomarker. It can evaluate the severity of liver disease and the risk of death. One day, we may be able to choose patients according to the status of cytolysin and carry out tailor-made treatment. "
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