小鼠实验 z-bo 2020-11-05 400

　　In order to protect the intestinal bacteria during illness, a special sugar is produced in the intestine of sick mice to serve as food for the microbiota and maintain a healthy microbial balance. This protective mechanism also seems to help resist other harmful pathogens, and its destruction may play a role in some human diseases such as Crohn's disease.

　　The senior author of the paper, Dr. Alexander Chervonsky, Chairman of the Immunology Committee of the University of Chicago, said: "In the case of illness, the host and their intestinal flora are affected, but the host protects this mutually beneficial relationship.

　　When faced with systemic diseases, animals will not search for food, but will eat less to save energy and deprive pathogens of nutrients. But this may harm the beneficial bacteria in the intestines, which play an important role in health and disease.

　　In order to explore the mechanism by which the microbiota is supported during the disease process, Chervonsky and his research team focused on the potential internal resource generated by the host-L-fucose (L-fucose). Studies have confirmed that this sugar can affect intestinal bacteria. The host cannot use L-fucose as an energy source, but when it is combined with protein, the flora can use it as a food source. Under normal circumstances, the small intestine of mice hardly produces L-fucose.

　　The research team exposed several different mice to molecules that mimic a systemic infection. The mice fell ill, their food intake and drinking water were reduced, and their weight was reduced. A few hours after the disease was induced, the researchers observed the production and presence of L-fucose on almost all surfaces of the small intestine. This effect is only seen in response to disease.

　　The researchers then tested genetically engineered mice lacking Fut2, which is responsible for the production of L-fucose. Mice lacking Fut2 remain healthy under normal conditions, but after induction of the disease, their weight recovery is much slower than their normal counterparts. Only mice with complete intestinal flora and capable of producing L-fucose can recover effectively.

　　Chervonsky said: “Mice that can produce L-fucose recover better than mice that cannot produce L-fucose. If you remove the bacteria, this effect will disappear.”

　　The research team used genetic analysis to confirm that the production of L-fucose metabolically affects intestinal bacteria. They pointed out that sick mice lacking Fut2 had significantly higher expression of harmful microbe genes than normal mice. The researchers speculated that the production of L-fucose somehow prevented opportunistic bacteria from expressing toxic genes. They exposed mice to a mild bacterial pathogen and induced the disease four days later. In this case, mice lacking Fut2 lost significantly more body weight than normal mice, indicating that the production of L-fucose helped the host resist other harmful pathogens.

　　Interestingly, about 20% of humans lack a functional gene that produces L-fucose. This problem is related to inflammatory bowel disease called Crohn’s disease.

　　Chervonsky said: “We speculate that without L-fucose, the activity of disease-causing genes cannot be blocked. This is why bacteria play a role in Crohn’s disease. Whether we can apply it to treatment in the future still needs Further research."