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Mothers Pass a Unique Set of Breast Milk Antibodies to Their Babies

A mother breastfeeding.
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Scientists at the University of Pittsburgh (Pitt) School of Medicine discovered that a mother’s breast milk comprises a unique set of antibodies – specific to her – which are stable throughout lactation and across pregnancies. The study is published in the Journal of Experimental Medicine.

Antibodies are obtained through breast milk

Human breast milk contains thousands of bioactive molecules, including antibodies, which support the development of a newborn baby’s immune system. The antibody profile of a mother’s milk is unique and might explain why some babies are more vulnerable to infections and serious conditions such as necrotizing enterocolitis (NEC), the new study suggests.

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NEC is a dangerous gastrointestinal condition that largely affects premature babies. It is characterized by inflammation of the intestinal tissue, which can lead to tissue necrosis and the formation of a hole in the intestinal wall. The cause of NEC remains unknown, but it may be associated with the immaturity of the newborn’s digestive system. The condition, which occurs more frequently in babies fed formula milk compared to breast milk, has also been linked to a family of bacteria known as Enterobacteriaceae.

In the gut, immunoglobulin A (IgA) antibodies bind to bacteria. Previously, Dr. Timothy Hand, associate professor of pediatrics and immunology at Pitt’s School of Medicine and UPMC Children’s Hospital of Pittsburgh, conducted a study analyzing and comparing fecal samples of healthy babies and preterm infants with NEC. The team identified that breast milk-fed babies had more IgA-bound gut bacteria compared to babies that developed NEC and had likely received formula milk.

“It’s been well known for a decade that babies who get NEC have particular bacteria – Enterobacteriaceae – in their guts, but what we found is that it’s not how much Enterobacteriaceae there is, but whether it’s bound to IgA that matters. And that’s potentially actionable,” Hand said. He hypothesized that babies demonstrated varied susceptibility to NEC because mothers pass down different antibody profiles to their infant through their breast milk.

Individual mothers’ antibody profiles look completely different

To explore this hypothesis, Hand and colleagues obtained samples of donor breast milk from the Human Milk Science Institute and Biobank in Pittsburgh and Mommy’s Milk Human Milk Research Biorepository in San Diego.

Using arrays of different species of bacteria, they measured which strains the donors’ antibodies bound to. “Individual donors’ antibody profiles looked completely different, which is what we had expected, but were able to show for the first time,” Hand described. “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.”

Over the course of a breastfeeding journey, the molecular composition of a mother’s milk changes. Does the antibody profile also change? When comparing breast milk from the same donors over a period of time, and across multiple pregnancies, Hand and team found the antibody profile to remain “remarkably” stable. “This suggests that when B cells arrive in the breast tissue, they don’t leave. This is important for understanding how babies acquire immunity and how they deal with infections,” Hand explained.

The team also questioned whether the antibody profile of breast milk is different for babies that are delivered preterm. The data from this study suggests not, Hand said: “Some B cells move to the mammary gland during the third trimester, so we wondered if a person delivers before this trimester is complete, would their milk have fewer antibodies. The good news was that we found no difference: Individuals who deliver pre-term have just as many antibodies and the same diversity as those who deliver full-term.”

Hand noted that the research highlights a potential Achilles’ heel of using maternal antibodies to protect infants – not all women have the same antibodies, and the antibodies do not change in response to what is occurring in the infant’s intestine. “Therefore, if maternal antibodies are not initially protective, that protection is not going to develop,” he said in a conversation with Technology Networks.

As a next step, the team would like to measure how diversity impacts breast milk antibodies. A limitation of the current study, Hand emphasized, is that the donor sample was not representative of the American population as a whole. “We have begun collaborations to look at much more diverse cohorts of women,” he concluded.

Dr. Timothy Hand, associate professor of pediatrics and immunology, was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

Reference: Johnson-Hence CB, Gopalakrishna KP, Bodkin D, et al. Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A. J Exp Med. 2023;220(8):e20220839. doi: 10.1084/jem.20220839