Key biological pathway in breastmilk that protects babies against respiratory infections discovered

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QIMR Berghofer researchers have found how breastmilk supports infant immunity via a protein called osteopontin, in a study which also identifies a potential way of mimicking this protective effect in baby formula. The findings, published today in the prestigious journal Cell, reveal osteopontin triggers a cascade of biological signals that support immune cell development in a baby’s liver and lungs, and help protect against potentially deadly respiratory infections.

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From: QIMR Berghofer

QIMR Berghofer researchers have found how breastmilk supports infant immunity via a protein called osteopontin, in a study which also identifies a potential way of mimicking this protective effect in baby formula.

The findings, published today in the prestigious journal Cell, reveal osteopontin triggers a cascade of biological signals that support immune cell development in a baby’s liver and lungs, and help protect against potentially deadly respiratory infections.

Scientists have long known that there are high levels of osteopontin in breast milk in the first weeks post-partum, but how it influences infant health has been a mystery.

Professor Simon Phipps from QIMR Berghofer’s Respiratory Immunology Labsaid it was remarkable to see the impact osteopontin had on lung cell health in their preclinical models.

“We looked at the infant lung cells that line the airways when the osteopontin was missing. It was like night and day,” Professor Phipps said.

"We observed that the osteopontin affected the infant’s microbiota composition, which in turn led to an increasein the production of bacterial metabolites, which act like hormones.  By acting on cells in both the liver and the lungs, the metabolites turned on growth factors which boosted the infant’s immune system”

In a second major finding, the team discovered that a drug already used to treat type 2 diabetes called rosiglitazone could mimic the effects of osteopontin by activating the same immune-supporting pathway.

"We identified that one of the metabolites acts on the same molecule as an approved drug called rosiglitazone. Remarkably, rosiglitazone had a similar protective effect against respiratory infections in our preclinical models,” Professor Phipps said.

Some infant formula contains cow’s milk osteopontin, but not at the levels seen in human breastmilk.

The discovery raises the possibility of developing new approaches to support immune development in infants and could inform future improvements to infant formula products.

As osteopontin increased immune regulatory pathways, Professor Phipps says it may also help prevent the onset of allergic diseases such as eczema and asthma, although this remains to be formally tested.

“Our study adds to growing scientific understanding of the complex bioactive components in human milk and how they influence infant development during these critical windows in early life”, Professor Phipps said.

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Supplementary Information QIMR Berghofer, Web page Explainer Video and images
Journal/
conference:
Cell
Organisation/s: QIMR Berghofer, The University of Queensland, Queensland University of Technology (QUT), Murdoch Children's Research Institute (MCRI), The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, La Trobe University
Funder: NHMRC, Nestle
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