Before coming to the University of Pittsburgh to complete her PhD in human genetics, Kathyayini Gopalakrishna spent three years working as a physician in a South Indian neonatal intensive care unit (NICU).

There, Gopalakrishna treated some preterm infants struggling with necrotizing enterocolitis (NEC), a life-threatening condition in which the underdeveloped intestines of newborns are unable to fight off bacteria. It’s treated either with heavy-duty antibiotics or, in cases where the invader kills its host tissue, by removing part of the intestine—drastic surgery that can result in lifelong side effects.

Scientists still don’t fully understand the precise causes of NEC, making any potential prevention or protection worth exploring. But breast milk seemed to be a possible X factor.

“I had personally seen babies [with NEC] improve a lot when they were fed with mother’s milk,” she says. Though breast milk has long been promoted globally to minimize various known health risks in infants, much remains a mystery about the specific protective mechanics of the most homemade beverage. Researchers did know that preterm formula-fed infants are three to four times more likely to develop NEC than preterm infants who are tube-fed breast milk.

Gopalakrishna decided to work with Pitt’s Timothy Hand, a PhD associate professor of pediatrics and of immunology, to find out how breast milk increased positive outcomes in her tiny patients. (She is now a postdoctoral fellow at the California Institute of Technology.)

“As a physician, you can have an impact, but it’s one life at a time,” says Gopalakrishna, who also has an MBBS. “In research, there’s an opportunity for you to impact thousands of lives at a time.”

In 2019, Gopalakrishna was the lead author on a Nature Medicine paper that identified an antibody necessary to prevent NEC in infants.

The Hand lab team built on that finding with a study led by Chelseá Johnson-Hence, an MD who completed a neonatal-perinatal medicine fellowship at Pitt and is now an assistant professor at UT Southwestern Medical Center.

In 2023, the researchers reported in the Journal of Experimental Medicine that premature infants who don’t develop NEC are protected by specific antibodies in breast milk—and that not all breastfeeding parents have them to give. The paper looked at the ability of antibodies in donated breast milk samples to bind to Enterobacteriaceae, the bacteria that, unchecked, cause the majority of NEC cases.

They found that every donor’s milk sample had a unique binding response, though individual donors remained consistent within and across pregnancies. That is, whether or not breastfeeding confers protection against NEC depends, pretty randomly, on whether the parent has previously encountered the bacteria that trigger the antibodies to fight it.  

“The idea that different people have different antibodies is not controversial,” says Hand, the paper’s senior author. “But nobody had ever shown it in breast milk before.”

The team developed a methodology, which they’ve patented, to determine the specificity of antibodies from maternal milk samples.

In their studies, the team saw “huge variation,” Gopalakrishna says, in terms of which donor antibodies bound effectively to the bacteria they were studying. “There was no uniformity,” she says. “It was all depending on what the mother has seen throughout her life.”

A global review in 2020 estimated that 7% of babies with very low birthweight admitted to the NICU will develop NEC. The new findings suggest a path toward making the disease rarer.

In the short term, if parental milk is unavailable, donated breast milk is statistically preferable to formula, Hand says. Looking forward, premature infants could perhaps have NEC-fighting antibodies routinely added to their tube-fed diet.

“We as a field are now very good at making monoclonal antibodies,” says Hand.

Those potential solutions will only become clearer as their work continues. The researchers are looking beyond NEC and trying to understand how the components of breast milk, especially antibodies, shape the development of the newborn microbiome. Scientists already know that breastfed infants have a decreased likelihood of developing allergies and asthma.

“It’s opened up a whole new area of research for us,” Hand says. “You can learn so much about how the immune system is responding to bacterial colonization in the intestine; you’re born sterile, then you have to learn to deal with all of these different bacteria.”

Read more from the Winter 2024 issue.