Johns Hopkins ’study shows that a mother’s diet may stimulate the immune systems of premature babies

Medical researchers have long realized that the diet of a pregnant mother has a major impact on the development of the fetal immune system and that babies – especially those born prematurely – have a stronger ability -fast – receiving breast milk to fight against diseases, suggests that even after childbirth, maternal diet is important. However, the biological mechanisms behind these connections have been unclear.

Now, in a study published on February 15, 2021, in the journal Nature Communication, a Johns Hopkins Medicine research team reports that pregnant mice fed a molecule-rich diet found abundantly in cruciferous vegetables – such as broccoli, Brussels sprouts and carrots – gave birth to protected pups stronger against necrotizing enterocolitis (NEC). NEC is a dangerous infectious condition that destroys a baby’s intestinal lining, making it one of the leading causes of mortality in premature babies.

The team also found that breast milk from these mothers continued to provide immunity against the NEC of the children.

Seen in as many as 12% of newborns weighing less than 3.5 pounds at birth, NEC is a rapidly progressing gastrointestinal emergency and is usually caused by harmless gut bacteria. attacking the undeveloped wall of the baby’s colon prematurely, causing inflammation that can eventually destroy healthy tension at the site. If enough cells become necrotic (die) until a hole is formed in the intestinal wall, the bacteria can enter the bloodstream and cause life-threatening sepsis.

In earlier mouse studies, researchers at Johns Hopkins Medicine showed that NEC results when the undeveloped intestinal lining in premature infants produces higher-than-normal amounts of a protein called hole-like receptor 4 (TLR4). TLR4 in full-term infants binds to bacteria in the gut and helps to keep track of the microbes. However, in premature infants, TLR4 can act as an immune system modifier, with an oversupply of the protein leading to error by directing the body’s immune mechanisms against disease to attack the intestinal wall instead. .

“Based on this understanding, we designed our most recent study to see if indole-3-carbinole, or I3C for short, could be a chemical fertilizer common in green leafy vegetables and known to degrade TLR4 production, fed to pregnant mice, bypassing their unborn children and then protecting them against NEC after birth, “says senior study author David Hackam, MD, Ph.D., chief surgeon at Johns Hopkins Children’s Center and professor of surgery at Johns Hopkins University School of Medicine. “We also wanted to see if I3C in breast milk could maintain that protection as the babies grow.”

In the first of three experiments, Hackam and his colleagues attempted to induce NEC in 7-day mice, half of which were born from I3C-feeding mothers who came from broccoli during pregnancy and half from mothers feeding a diet without I3C. They found that those born to mothers who received I3C during pregnancy were 50% less likely to develop NEC, even with their immune systems still abnormal at a week after birth.

The second trial examined whether breast milk with I3C could continue to protect baby mice against NEC. To do this, the researchers used genetically bred mice without the binding site of intestinal cells for I3C called the aryl hydrocarbon receptor (AHR).

When puppies with AHR deficiency received breast milk from mice fed a diet containing I3C, they were unable to process the fertilizer. Thus, they developed NEC 50% more often than baby mice that had the I3C receptor.

The researchers say this shows in mice – and suggests in humans – that AHR must be applied to protect babies from NEC and that what a mother eats during breastfeeding can – in this case, I3C – affects the ability of its milk strengthens a child’s immune system.

In empirical studies, Hackam and his colleagues looked at the amount of human-acquired AHR obtained from infants undergoing surgery for severe NEC. They found significantly lower than normal levels of the receptor, suggesting that reduced AHR predisposes infants to the disease.

Finally, the researchers investigated a modern drug that could be given to pregnant women to reduce the positive side effects of AHR and reduce the risk of NEC if premature birth occurs . After screening in fertilized mice a combination of compounds already approved by the U.S. Food and Drug Administration for other clinical uses, the researchers noted that one, called A18 (clinically known as A18), was administered. lansoprazole, a drug approved for the treatment of gastrointestinal hyperacidity), activates the I3C receptor, restricts TLR4 signals and prevents gut bacteria from entering the intestinal wall.

To demonstrate the appropriateness of what they saw in mice, the researchers tested A18 in the laboratory on human intestinal tissue removed from patients with NEC and found the drug taking -out similar protection results.

“These decisions allow us to think about developing a maternal diet that not only promotes the full growth of a baby, but contributes to a developing fetus immune system and, therefore, the risk from NEC if the baby is born prematurely. , “said Hackam.

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Along with Hackam, members of the Johns Hopkins Medicine team are Peng Lu, Yukihiro Yamaguchi, William Fulton, Sanxia Wang, Qinjie Zhou, Hongpeng Jia, Mark Kovler, Andres Gonzalez Salazar, Maame Sampah, Thomas Prindle Jr. and Chhinder Sodhi. Peter Wipf at the University of Pittsburgh also participated in the study.

The research was supported by grants from the National Institutes of Health R01GM078238, R01DK117186 and T32 DK00771322, and the Garrett Fund for Medical Research.

Hackam, Wang, Sodhi and Lu have filed a patent application for the use of AHR agonists in the prevention and treatment of NECs. The remaining authors do not declare competing interests.