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Breastmilk antibody protects preterm infants from deadly intestinal disease

June 17, 2019

PITTSBURGH, June 17, 2019 - A new study from the University of Pittsburgh and UPMC Children's Hospital of Pittsburgh finds that an antibody in breastmilk is necessary to prevent necrotizing enterocolitis (NEC)--an often deadly bacterial disease of the intestine--in preterm infants.

Immunoglobulin A (IgA) antibodies bind to bacteria in the gut, and, according to the study, the more bacteria that's tied up with IgA, the less likely babies are to develop NEC. Since preterm infants get IgA only from mothers' milk in their fragile first weeks of life, the authors emphasize the importance of breastmilk for these babies. The study appears today in Nature Medicine.

"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," said senior author Timothy Hand, Ph.D., assistant professor of pediatric infectious diseases at the R.K. Mellon Institute for Pediatric Research and Pitt's School of Medicine.

The researchers looked at fecal samples from 30 preterm infants with NEC and 39 age-matched controls. Overall, breastmilk-fed babies had more IgA-bound gut bacteria than their formula-fed peers, and those who developed NEC were more likely to have been formula-fed.

Tracking these infants' gut microbiomes over time, Hand's team found that for the healthy babies, Enterobacteriaceae was largely tied up by IgA, allowing diverse bacterial flora to flourish. But for the NEC infants in the days leading up to diagnosis, IgA-unbound Enterobacteriaceae was free to take over.

To demonstrate causation between IgA and NEC, Hand and his team used a mouse model.

"Mice, when they're born, are equivalent in their intestinal development to a human baby born at 24 weeks," said lead author Kathyayini Gopalakrishna, M.D., a Ph.D. student in the Pitt Graduate School of Public Health's Department of Human Genetics, "so they're a perfect model to study NEC in preterm infants."

The researchers bred mice that couldn't produce IgA in their breastmilk. Pups reared on IgA-free milk were just as susceptible to NEC as their formula-fed littermates. So, breastfeeding in and of itself is not sufficient for NEC prevention. The milk must contain IgA to confer this specific benefit.

But the solution for NEC may not be as simple as putting IgA into formula, Hand said. Because breastmilk has other benefits beyond IgA, donor milk is still the best option to fill the gap when breastfeeding or providing pumped maternal milk isn't an option.

"What we showed is that IgA is necessary but may not be sufficient to prevent NEC," Hand said. "What we're arguing is that you might want to test the antibody content of donor milk and then target the most protective milk to the most at-risk infants."
-end-
Other authors on the study include Benjamin Macadangdang, M.D., Ph.D., Justin Tometich, Robyn Baker, Junyi Ji, Ansen Burr and Congrong Ma, M.S., from UPMC Children's Hospital; Matthew Rogers, Ph.D., Brian Firek, M.S., and Michael Morowitz, M.S., from Pitt; and Misty Good, M.D., from Washington University School of Medicine.

Funding for this work was provided by the National Institutes of Health (grants K08DK101608, R03DK111473 and R01DK118568), March of Dimes Foundation (grant 5-FY17-79) and the R.K. Mellon Foundation Institute for Pediatric Research.

To read this release online or share it, visit http://www.upmc.com/media/news/061719-hand-iga-breastmilk [when embargo lifts].

About the University of Pittsburgh Schools of the Health Sciences

The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the UPMC (University of Pittsburgh Medical Center). Together, their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. Since 1998, Pitt and its affiliated university faculty have ranked among the top 10 educational institutions in grant support from the National Institutes of Health. For additional information about the Schools of the Health Sciences, please visit http://www.health.pitt.edu.

About UPMC Children's Hospital of Pittsburgh

Regionally, nationally, and globally, UPMC Children's Hospital of Pittsburgh is a leader in the treatment of childhood conditions and diseases, a pioneer in the development of new and improved therapies, and a top educator of the next generation of pediatricians and pediatric subspecialists. With generous community support, UPMC Children's Hospital has fulfilled this mission since its founding in 1890. UPMC Children's is recognized consistently for its clinical, research, educational, and advocacy-related accomplishments, including ranking 15th among children's hospitals and schools of medicine in funding for pediatric research provided by the National Institutes of Health (FY2018).

http://www.upmc.com/media

Contact: Erin Hare
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E-mail: HareE@upmc.edu

Contact: Andrea Kunicky
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E-mail: KunickyA@upmc.edu

University of Pittsburgh

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