The likely cause of babies developing a life-threatening gut disease found

Necrotizing Enterocolitis (NEC), a severe inflammatory gastrointestinal disorder, primarily targets premature infants. It is associated with a group of bacteria known as Enterobacteriaceae. Formula-fed babies are approximately 2 to 4 times more likely to develop NEC compared to those who are breastfed.

According to a recent study in the Journal of Experimental Medicine by the University of Pittsburgh School of Medicine, it has been discovered that each individual’s breast milk possesses a distinct combination of antibodies. These antibodies have shown impressive stability, persisting throughout the course of breastfeeding and across multiple pregnancies.

The study provides valuable insights into early infant immunity, which is primarily shaped by the antibodies present in breast milk. This knowledge sheds light on the varying resistance to infections in infants and why certain babies develop a severe intestinal disease known as necrotizing enterocolitis (NEC).

The principal investigator of the study, Dr. Timothy Hand, an associate professor of pediatrics and immunology at Pitt’s School of Medicine and UPMC Children’s Hospital of Pittsburgh, shared his findings.

“While each milk donor in our study had very different antibody profiles from one another, we found that antibodies from the same donor were quite similar over time — even across the span of months,” he explained.

This suggests that if a parent lacks certain antibodies—such as those against NEC—these won’t be passed on to their baby, offering a potential explanation for the selective occurrence of NEC in infants.

NEC is a severe inflammation of the gut primarily affecting preterm babies and has been associated with a bacterial group called Enterobacteriaceae. It is 2 to 4 times more prevalent in babies fed with formula than breast milk.

Before an infant’s immune system is fully developed, they are safeguarded from harmful bacteria by antibodies transmitted through the mother’s placenta and breast milk. These antibodies latch onto bacteria in the intestine, preventing them from causing harm to the baby.

Earlier research by Dr. Hand and his team revealed that healthy infants’ fecal samples primarily contained Enterobacteriaceae bound by maternal antibodies. In contrast, babies who later developed NEC showed more unbound bacteria. The variance in babies’ immunity to NEC could be due to the diverse antibodies passed on by different mothers, a hypothesis supported by the new study.

In this study, the research team analyzed breast milk samples from various donors via the Human Milk Science Institute and Biobank in Pittsburgh and the Mommy’s Milk Human Milk Research Biorepository in San Diego. They identified the bacteria strains that were targeted by each donor’s antibodies.

“Individual donors’ antibody profiles looked completely different, which is what we had expected but were able to show for the first time,” said Dr. Hand. “During pregnancy, B cells travel from the intestine to the mammary gland, where they start making antibodies. The mom is trying to protect her infant using antibodies that she uses to protect her own intestine. Different women have led different lives, have different microbiomes and have encountered different infections, so it makes perfect sense that breast milk antibodies would reflect that variability.”

The team also compared breast milk from the same donors over time and across multiple pregnancies to investigate potential changes in antibody composition. They found that the antibodies remained stable, suggesting a potential mechanism for how babies gain immunity and respond to infections.

Another aspect of the study was investigating if premature delivery affected the antibody content in breast milk. They found that preterm mothers had just as diverse and plentiful antibodies in their milk as those who had full-term pregnancies.

It’s known that a mother’s own milk is optimal for preventing NEC in preterm babies, and when not available, donor milk serves as a crucial alternative. This milk is pasteurized to eliminate bacteria, but the impact on the antibodies was unclear. The team discovered that pasteurization decreases the antibody levels in donor milk, indicating infants fed with donor milk may receive fewer antibodies than those who get milk directly from their mothers. However, Dr. Hand emphasizes more research is needed to establish the protective antibody levels against diseases like NEC.

Future research may focus on understanding which bacteria pose the greatest risk for preterm infants susceptible to NEC, leading to the development of antibodies that could be added to formula or breast milk to enhance immunity.

Source: 10.1084/jem.20220839

Image Credit: Shutterstock