: Unravelling the role of breast milk ether lipids in modulating immune function in early life

Summary In this project we will combine our lipidomics expertise with our unique mouse models of ether lipid modification to define the role of breast milk ether lipids in modulating immune function in infants.

Project Details

Breastfeeding, the biological norm of feeding babies, provides numerous health benefits to babies. Infant-formula-feeding is thought to be inferior to breastfeeding because human milk provides specific and non-specific factors that have long-term consequences for early metabolism and the development of diseases (1). However, the 20th century witnessed an increase in formula feeding. Currently, only 35% of infants are exclusively breastfed in the first six months of their life.

Lipids make up 3-5% of the composition of human breast milk. Besides providing energy, breast milk lipids are also necessary for the infant growth and development (2). We have recently performed the largest plasma lipidomic profiling study of mothers and infants from the Barwon Infant Study (BIS) and observed that ether lipid species were markedly elevated in infants who were breastfed compared to those who were not. We have also profiled breast milk samples available from BIS and several infant formulae and found that breast milk has a clearly distinct lipidome compared to infant formulae. In particular, breast milk has significantly higher ether lipid content compared to infant formulae. Ether lipids are a class of lipids with unique structural feature and are thought to have anti-oxidant, anti-inflammatory and immunomodulatory properties (3).

We hypothesise that breast milk ether lipids can modulate immune cell function and thereby help in the development of immunity in infants. The aim of this project is to determine the effects of modifying the ether lipid content of milk (a) on the immune cell lipidomes and (b) on the susceptibility of these immune cells to pathogenic stimuli such as oxidative stress and inflammation in a murine model.

We will generate a unique genetically modified mouse model to deplete the content of ether lipids in mouse milk. We will also supplement pregnant and lactating mice with alkylglycerols (naturally occurring precursors that can be metabolised into endogenous ether lipids) to modify the milk ether lipid content in different magnitudes. We will characterise the milk samples using our state of the art liquid-chromatography mass spectrometry based lipidomics method to confirm the modification of ether lipid content in mouse milk. We will also characterise the lipidomes of plasma, different immune cell types and several tissues of newborn mouse pups (before they transition onto solid food) to examine how modification of ether lipid content in milk affects pups’ endogenous lipidomes. We will also examine the susceptibility of different immune cell sub-types from newborn pups exposed to different levels of milk ether lipids to oxidative cell death and inflammation.