Scientists dissect the microbial clues of liver diseases

November 19, 2019 / BIOON / -- in 1984, microbiologist Barry Marshall studied himself as an experimental object In order to prove that bacteria can cause gastric ulcer, he drank the contents of the flask containing Helicobacter pylori Recently, a report was published in the international journal Nature In the previous study report, researcher Duan et al Said that some extreme behaviors should not be taken to investigate the relationship between bacteria and disease Nevertheless, the researchers carefully analyzed a liver disease called alcoholic hepatitis After the study of mice and the analysis of body samples of patients with the disease, the researchers provided striking evidence to clarify A suspected bacterial culprit may have been involved in the disease Alcoholic hepatitis is a disease related to a large amount of alcohol intake, which is difficult to treat Previous studies on mice have shown that enterobacteria Enterococcus faecalis may be involved in the occurrence of the disease However, Enterococcus faecalis is generally considered as an "old friend" in the intestines of many animals, which is usually in the feces of healthy people The proportion is less than 0.1% However, after antibiotic treatment, the level of enterococci in the intestine will increase and become one of the most common microbial types in the intestine Enterococcus faecalis will infect the blood, heart, bladder, brain and teeth (after root canal operation) Photo source: Duan et al Doi: 10.1038/s41586-019-1742-x Researcher Duan et al Analyzed fecal samples of human beings Enterococcus faecalis was found in the feces of about 80% of patients with alcoholic hepatitis, and about 30% of Enterococcus faecalis had a gene encoding cytolysin In addition, compared with people without alcoholic hepatitis, the level of Enterococcus faecalis in the fecal samples of patients with alcoholic hepatitis was the same as that of the former Almost 300 times, but it doesn't prove that the disease is caused by Enterococcus faecalis Research evidence shows that bacteria in feces The presence of cytolysin is related to the mortality of patients 89% of the people with cytolysin in stool samples died within 180 days after admission, while only 3.8% of the patients with alcoholic hepatitis who lack cytolysin in stool samples died The researchers then analyzed the association between liver disease and Enterococcus faecalis in mice These animals were transplanted with Enterococcus faecalis, which can produce or cannot produce cytolysin Then some of them were fed with a high alcohol diet, and the other were given a nonalcoholic diet Only mice fed with a high alcohol diet and mice implanted with Enterococcus faecalis, which can produce cytolysin, came out Now there is liver damage Later, the researchers used sterile mice to study, and transplanted fecal samples from patients with alcoholic hepatitis to sterile mice These fecal samples contained Enterococcus faecalis that could or could not produce cytolysin The results showed that these mice showed a certain degree of liver damage and liver cell death after transplanting fecal samples containing cytolysin in mice with high alcohol diet There was no evidence of liver damage in mice on a high alcohol diet that lacked cytolysin In order to understand the mechanism of inducing disease, researchers isolated liver cells from animals and found that cell death in response to the exposure of cytolysin may have some sign dependence Whether the mice received a high alcohol diet or not, their response to cytolysin was the same, which showed that alcohol was not induced by damaging liver cells Alcoholic hepatitis occurs because alcohol increases the permeability of the intestinal lining, allowing Enterococcus faecalis, which produces cytolysin, to enter the liver and cause symptoms Because the current treatment of alcoholic hepatitis is very limited, researchers want to investigate whether we can develop an effective strategy through in-depth study of phages Compared with antibiotics, phages have a high specificity advantage, which can avoid killing beneficial bacteria in the body In addition, due to the fact that the surface of human cells and bacteria There are essential differences on the surface of cells, so phages do not infect animal cells or human cells; in the past 100 years, phages have been used to remove Salmonella and Shigella in the infected human intestinal tract, and they can also help to remove pathogenic Clostridium spp previous studies have suggested that researchers may be able to use phages to remodel intestinal microflora in the future The composition of organisms, thus producing a variety of beneficial flora to improve the health of the body and reduce the risk of human disease At present, researchers are discussing whether phages targeting Enterococcus faecalis can be used to treat a variety of human diseases Phages can kill drug-resistant Enterococcus faecalis related to human bone and wound infection In addition, they can also be used in the food industry to help eliminate Enterococcus faecalis in foods such as cheese, so as to effectively inhibit the production of toxic waste In order to test whether a method can be developed to specifically remove the Enterococcus faecalis producing cytolysin from the mouse body, the researchers identified a phage that can target Enterococcus faecalis but does not affect other intestinal flora They found that compared with transplantation, it can kill bacteria that do not often exist in the animal body The liver damage of mice receiving human fecal transplantation, high alcohol diet and targeting Enterococcus faecalis phage was lower This study analyzes the advantages of using bacteriophages to investigate the effects of microorganisms on diseases According to the researchers, bacteriophages can be used to identify pathogenic bacterial components, and they can also be used as a potential therapeutic option; of course, the researchers need to carry out clinical trials later Further tests are included to assess whether phage therapy can be used in humans, such as targeting Enterococcus faecalis in the intestine before liver transplantation In the study of researcher Duan et al., the researchers used phages to treat a disease with pathogenic factors usually existing in intestinal flora, although many phage researches focused on the use of these viruses (phages) to treat bacteria with antibiotic resistance Related diseases, but Duan et al's research has expanded the application of phage therapy There are many research evidences that intestinal microorganisms can affect the function of specific cells in the brain, and there are also studies to analyze whether these intestinal microflora play a key role in human brain diseases Maybe in the future, phage therapy is expected to become a new generation of anti-virus which is difficult to treat diseases at present Part of bacteriotherapy, but in fact, there may be many diseases that researchers do not realize are related to microbial components, and these diseases can often be solved by bacteriophage therapy Reference materials: [1] Martha R J clokie Microbial clubs to a liver disease, nature (2019) doi: 10.1038/d41586-019-03417-3 [2] Marshall BJ, Armstrong JA, mcgechie dB, et al Attempt to full Koch's posts for criminal campylobater Med J AUST 1985 APR 15; 142 (8): 436-9 [3] Yi Duan, Cristina llonte, Sonja Lang， et al Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease ， Nature (2019) doi：10.1038/s41586-019-1742-x