A new mouse study led by Johns Hopkins Children's Center researchers suggests a link between a high-fat prenatal diet and induction of potentially deadly symptoms of necrotizing enterocolitis (NEC) in premature babies.
Findings from the study, funded by the National Institutes of Health, were published April 15 in Cellular and Molecular Gastroenterology and Hepatology .
Each year in the U.S., an estimated 3,500 prematurely born infants develop NEC , an inflammation of the lining of the intestines that causes the tissue to die. An estimated 10% to 50% of infants die of the condition or develop long-term complications, including short bowel syndrome and neurodevelopmental impairment.
Although precise causes of NEC are unknown, postnatal risk factors include formula feeding and an imbalance in gut bacteria.
In addition, maternal conditions including obesity and diabetes during pregnancy have been linked to more severe cases of NEC.
For the new study, experts led by David Hackam, M.D., Ph.D., surgeon-in-chief and co-director of Johns Hopkins Children's Center, worked with mice to examine whether a high-fat diet in mothers could influence the development of NEC. They focused on high-fat diets because of known links between infants developing NEC and pregnant women with obesity and diabetes.
In their study, female mice were given a high-fat diet, consisting of 70% of calories from fat, or a standard diet, and mated with males fed a standard diet.
Mice with NEC born to mice that were fed high-fat diets were compared with mice with the intestinal condition born after their mothers were fed standard diets. All mice in the high-fat diet group had more severe symptoms of NEC and a 50% survival rate, compared with less intense symptoms and a 70% survival rate for those born to mothers in the standard diet group.
Those in the high-fat maternal diet group had poorly developed intestines — some with shorter intestinal structures and fewer protective cells that produce mucus — compared with those in the standard diet group.
To understand why maternal high-fat diet contributed to more severe NEC, the researchers took a closer look at the intestinal structure of mice in both groups. They found that mitochondria, energy-producing organelles in cells, were more damaged and had a more abnormal appearance in mice in the high-fat group than those in the standard diet group.
Next, to understand the reasons for the mitochondrial injury, the researchers examined gene expression in cells lining the intestines. They found that mice in the high-fat maternal diet group had more activity in structural genes, including Sost and Btnl9, which are responsible for regeneration of the intestinal lining and immune system health, respectively.
Also in those born to the high-fat group, the researchers found reduced gene expression in the Nqo1 and Gsta1 genes, which are linked to antioxidant responses, and the Kiss1 and Gsdmc4 genes, which maintain intestinal lining immunity and structure.
Because mice and humans share some biological and genetic functions, "It's possible that these findings in mice could also apply to human mothers and their babies," says Hackam. "The good news is that a well-balanced diet is always a healthy decision for a mother and her baby."
Based on these findings, Hackam says the next steps are to focus on how mitochondrial gene pathways could be used as targets for new drug development to treat NEC, either in the presence or absence of a high-fat diet during pregnancy.
Other authors in this study include Koichi Tsuboi, Hee-Seong Jang, Pranav Prakash, Brian Kwon, Sanxia Wang, Menghan Wang, Thomas Prindle, Jr., William B. Fulton and Chhinder P. Sodhi with Johns Hopkins.
No authors declared conflicts of interest under Johns Hopkins University School of Medicine policies.
David J. Hackam is funded by National Institutes of Health R35 GM141956. David J. Hackam is also supported by the Garrett Fund for the Surgical Treatment of Children at The Johns Hopkins University.
