Science Sub-Journal: What causes intestinal disorders in premature infants?

In a mouse study published today in the journal Science translmedicine, a medical research team at Johns Hopkins University provided information that may have caused necrotizing enterocolitis (NEC) so far.

Symptoms in preterm infants include bloating and food intolerance-these are caused by bowel dyskinesia, the senior author of the study, the chief surgeon of the Johns Hopkins Children's Center, and the Johns Hopkins University School of Medicine Surgery Professor David Hackam said

Hackham and his colleagues say that it seems logical that the enteric nervous system and the glial cells that support its function play such a key role in the formation of NEC

In their study, the researchers also discovered the overproduction of a protein called toll-like receptor 4 (TLR4)-previous research by Johns Hopkins Medicine has shown that this protein is related to the pathogenesis of NEC -Triggered the loss of intestinal glial cells

"This discovery allows us to test a compound in mice that can'activate' the intestine by preserving intestinal glial cells and their ability to produce BDNF, thereby restoring intestinal motility.

Among newborns born before 37 weeks of gestation, up to 12% of newborns develop NEC, which is a rapidly developing gastrointestinal emergency.

In early mouse studies, researchers at the Johns Hopkins School of Medicine showed that NEC is produced when the underdeveloped intestinal lining of premature babies produces higher than normal amounts of TLR4

"Knowing this, we designed our current study to see if TLR4 is related to the loss of intestinal glial cells, and if so, how it paves the way for the development of NEC," Kovler said

Based on their experimental results, the researchers were able to provide five areas of evidence, showing that intestinal dyskinesia (tlr4 affects the loss of intestinal glial cells) is a key factor in the pathogenesis of NEC:

• Compared with wild-type (genetically normal) mice, three different strains of mice without intestinal glial cells showed impaired intestinal motility, and in turn, NEC was more severe

  
  

• Mice cultured with intestinal glial cells that cannot produce TLR4 did not lose glial cells, showed dyskinesia or developed NEC, indicating that TLR4 is a necessary condition for glial cell loss and is related to disease

  
  

• Administration of BDNF to glial-deficient mice can reduce the severity of NEC in animals, which indicates that the release of BDNF from intestinal glial cells helps protect the intestine from NEC damage

  
  

• When there is too much TLR4 in the intestinal wall, the release of BDNF will prevent the excess protein from sending a signal to the immune system to mistakenly attack healthy tissues

  
  

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The researchers also studied NEC-damaged intestinal tissues from wild-type mice, piglets, and human infants whose tissues were removed during surgery to treat NEC.

"Because we have shown that intestinal glial cells protect the intestines of animals from the devastating effects of NEC, it is reasonable to assume that a similar situation exists in humans," Hackham said
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"If one day we can repair this system and prevent premature infants from developing NEC by using intestinal glial cell therapy such as J11, then these small patients will have one less obstacle to overcome
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