Interaction Among Phage, Bacteria, and Health

  • As bacterial viruses, bacteriophages have been increasingly reported for their unique role in affecting bacterial diseases. Bacteriophages can directly control the composition and abundance of bacteria and indirectly affect the body's metabolism and immune system.

     

    The human body is like a movable culture medium with a large number of microorganisms, including symbiotic bacteria and bacterial viruses, of which symbiotic bacteria are the main components of the human microbiota, while bacterial viruses are usually called bacteriophages. These microbial groups do not exist in the human body in isolation, but interact with the body through mutually beneficial symbiosis, and form a unique and stable internal ecosystem. More and more studies have shown that these microorganisms that reside in the human body have a close influence on the health of the human body.

     

    Where do baby gut phages come from?

    The gut microbiota plays an indispensable role in maintaining the health of the body, the main function of which is to help the body digest and absorb the nutrients in food, and is closely related to the metabolism of the body, the occurrence of diseases, and the maturation of the immune system. Previously, attention to the gut microbiota was mainly focused on intestinal bacteria. Recent studies have found that as an important part of the gut microbiota, the proliferation and distribution of phages are closely related to the life state of the body.

     

    Studies found that there are almost no bacteriophages in the meconium of babies, or only a small amount of bacteriophage particles. But one month after the baby was born, the phage load increased sharply to 109 per gram of feces, which has aroused the curiosity of scientists about where these phages come from? To this end, the researchers collected 648 stool samples from 1-year-old children and isolated 900 strains of Escherichia coli. They found that more than 60% of Escherichia coli can spontaneously release temperate phages. In contrast, Fewer than a quarter of stool samples contain virulent phages, indicating that infant intestinal phages originated from bacteria that colonized the intestine early and contained mild phages.

     

    What are the characteristics of adult intestinal phages?

    In 2014, biologists discovered a new type of bacteriophage in the human intestine, named crAss bacteriophage, a large and ubiquitous phage family, existing in more than 50% of human individuals and distributed globally. The crAss bacteriophage mainly infects Bacteroides, one of the intestinal commensal bacteria, and the content in some individuals can reach more than 90% of the total enteroviruses. Scientists conducted a metagenomics study on the microbiome and virus group of 10 healthy adults within one year and found that the content of enteroviruses was as high as 108-1,010 per gram of feces, which were composed of more than 39,000 viruses. The viruses in the adult intestine mainly compose crAss-like bacteriophages, microviridae bacteriophages, and a small number of highly specific viruses. As age increases, the diversity and abundance of bacteriophages in the intestine grow gradually, and crAss-like bacteriophages occupy the majority in old age.

     

    Is phage therapy feasible?

     

    The potential of bacteriophages for the treatment of various diseases in the human body has been widely recognized. Crohn's disease is a typical chronic enteritis, which can repeatedly cause inflammation of the intestinal mucosa. Although the exact cause is still unclear, studies have shown that the predominant pathogen on the ileal mucosa of patients with this disease is an adherent invasive Escherichia coli (AIEC). In an animal model study, after AIEC intestinal infection mice were fed with three targeted and potent phages, the number of AIEC in the feces and intestines significantly reduced. More importantly, a single dose of phage cocktail is sufficient to reduce the occurrence of colitis within two weeks and prevent the symptoms of ulcerative colitis from worsening.

     

    Can alcoholic hepatitis also be treated with bacteriophages?

    The use of phage to target and eliminate pathogenic bacteria in the intestinal tract can treat intestinal diseases and be used to prevent or treat diseases outside the intestinal tract. Scholars have found that alcoholic hepatitis is positively related to the colonization of Enterococcus faecalis in the intestine, which can produce compound cytolysin that will be transferred to the liver after being produced in the intestinal tract, leading to liver damage, liver cell death, liver function decline, and ultimately an increase in mortality. After feeding the mouse model of Enterococcus faecalis infection with targeted potent bacteriophages, the colonization of Enterococcus faecalis in the intestine is significantly reduced, thereby reducing the production of cytolysin, and eliminating alcohol-induced liver damage, steatosis, and inflammation, indicating that the regulation of bacteria by bacteriophages in the intestine can have a comprehensive impact on the mammalian host.