Intestinal microbes can cause the production of rare immune cells in the intestine of animalsHite [1399] Publish time :2017-08-10

A statement that worries all the mothers is attracting people's attention that the rumors that are exposed to microbes are beneficial to us and can activate our immune system and avoid allergies such as asthma, autoimmune diseases, etc. Have the advantage. Now, a new study on the controversial concept of hygienic hypotheses suggests that microbes will have a beneficial effect from an unexpected path. Researchers have found that typical intestinal bacteria in mice can control a rare immune cell, thereby reducing asthma and rodent colitis.

      Scientists have embarked on a long discussion about this hygienic hypothesis and completed a new research work, which was reported online at this week's Science (http://scim.ag/Olszak) and achieved the highest click-through rate. "This is one of the most rigorous and mechanical studies I have seen in this field for so long," says Sarkis Mazmanian, a microbiologist at the California Technology Center in Pasadena. "The authors of this paper have established theoretical support for immunology," said Everett Meyer, a clinical immunologist at the Stanford University School of Medicine in California, who has discovered a few decades of unknown mechanism.

      This twenty years ago the proposed hygiene hypothesis concluded that the negative effects of modern society's anti-microbial warfare. This hypothesis that, in order to normal operation of the body, in our young immune system will need to accept microbial stimulation. Without these early stimuli, our immune cells will become more likely to stimulate inflammation and produce autoimmune responses in middle age, such as allergies, asthma, gastrointestinal irritation, and multiple tissue sclerosis. In addition, this hypothesis also explains why the children who grow up on the farm suffer from a lower probability of asthma and allergies: they are probably more or more than the concentration of bacteria in the city's children. "A general consensus that microbiological exposure can protect the body and avoid the development of different allergies and autoimmune diseases," says Anthony Honner, a pediatric immunologist at the California State University in San Diego.

      The tricky question is how the microbes provide a protective effect. Mice lacking normal microbial associated flora and pathogens provide Richard Blumberg and colleagues for the Boston Brigham Women's Hospital mucosal immunologist with an opportunity to unravel the mystery. These so-called sterile mice live in sterile squirrels for a lifetime, eating sterile foods, so they can not get the normal rodent intestinal symbiotic flora. Researchers have found that sterile mice are more susceptible to colitis (an enteric inflammatory disease) and asthma than comparable peptides that have colonized a large number of flora in the intestine. The number of "invariant natural killer T cells" (iNKT) found in the lungs and intestines of sterile mice was much higher than normal. These immune cells trigger an inflammatory response after monitoring specific microbes or their own synthetic special molecules (also known as antigens).

      This new study suggests that these cells play a crucial role in the environment of colitis and asthma. Blumberg and colleagues found that genetically modified mice lacking iNKT cells did not develop colitis even when they grew up in sterile environments. In addition, Blumberg's team treated these iNKT-containing rodents with antibodies that block cell-monitoring antigens, and can significantly prevent colitis from occurring in sterile mice.

      Samples of sterile mice were transferred to conventional squirrels in mice, and the researchers demonstrated the importance of early microbial exposure affecting the distribution of iNKT cells. The transferred sterile mice rapidly obtained the intestinal bacteria of the bacterial mice. Adult non-sterile mice did not reduce the number of iNKT cells in the colon after metastasis. However, when the researchers were transferred with sterile mice that had been pregnant, it was found that their offspring could be immersed in conventional bacteria after birth and found that the number of iNKT cells in neonatal mice was low after birth to growth. "From this study it is clear that iNKT cells are sensor cells that monitor intestinal bacterial flora and will respond to flora," Blumberg said.

      Researchers generally believe that the presence of intestinal bacteria can lead to an increase in the number of immune cells, Honer said, but the actual study found that the results are the opposite. "This is an exciting finding that runs counter to the routine understanding of the relationship between immune system development and microbial exposure." The mechanism behind this relationship may be related to an immune signal called CXCL16. Blumberg and colleagues show that the lack of intestinal bacteria triggers a large number of CXCL16 synthesis, which may stimulate iNKT cell aggregation.

     "The world is not sterile human," says Mitchell Kronenberg, an immunologist at the La Jolla Institute in California. "Because all of us have intestinal microbes, the next step in this study is to tell which Intestinal colonization has a beneficial effect on the immune system. "Kronenberg also said that by virtue of today's powerful DNA sequencing technology, we can also identify some difficult to detect the micro-organisms. Blumberg added that he and his colleagues are preparing to try to identify the special microorganisms that provide protection.

     "Although the results did not immediately help people with asthma more likely to breathe, but it instructed researchers to study a new treatment," says Mazmanian. "Inflammation is associated with too many cells and signaling molecules It is difficult to determine which metabolic pathway should be blocked, but by revealing that a cell can cause inflammation, the researcher can provide a point to lock the blocking target.

      In addition, the researchers said the findings provided more in-depth evidence to prove that too clean and sometimes lead to disease, even though our mother once told us to keep it clean. "This is another example of why microbiological exposure is so important to our immune system," Horner said.

      Editor's Note: From the above findings we can speculate that early exposure to newborn piglets or other animals beneficial micro-organisms, especially intestinal micro-organisms, will help the development of the intestinal immune system and improve pig's resistance to the disease. Although it is unclear which intestinal microbes have the greatest effect on the development of the intestinal immune system, we estimate that lactic acid bacteria, myxobacteria, and Clostridium butyricum should have these effects.


Olszak T., An D., Zeissig S., Pinilla Vera M., Richter J., Franke A., Glickman JN, Siebert R., Baron RM, Kasper DL, Blumberg RS Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function. Science DOI: 10.1126 / science. 1219328.

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