Breast-feeding has been linked to higher intelligence in later childhood compared with formula-feeding. Low birth weight infants benefit more in cognitive development from breastfeeding than full term infants. Morphometric brain imaging studies have revealed an increase in the volume of white and sub-cortical grey matter, and parietal lobe cortical thickness, which are associated with IQ in adolescents who were breastfed as infants compared to those who were exclusively formula-fed.
Currently, only ~35.4% of Australian infants are exclusively breastfed until ca. 6 mo. This means that >60% of Australian infants rely on infant formula during early neural development. Early-life nutrition refers to the critical period of the first 1000 days of life, which starts from conception and extends through pregnancy and the first two years of a child's life. This period is widely recognized as a window of opportunity for optimal growth, development, and a child's health and well-being throughout their life. Therefore, our study has the potential to impact neonatal care for all children, particularly those born premature, and reduce costs of health care and social services and will enhance the wealth of Australian societies.
Human milk oligosaccharides (HMOs) are the third most abundant class of biomolecules in mature human milk, after lactose and lipids, reaching levels ~20–25g/L in colostrum and 5–20g/L in mature milk (1, 2). More than 200 different HMOs have been identified (1), with ~10–20% containing the acidic sugar, sialic acid, so called sialylated HMOs. The remaining are neutral HMOs. Human milk contains ~100-1000 fold higher levels of HMOs than bovine milk or any infant formula. Breastmilk is the optimal and complete source of nutrition for infants during the first 4-6 months of life. Infant formula is the recommended alternative and the first choice for providing nutrition to infants who cannot be exclusively breastfed. However most infant formula is cow’s milk based missing critical nutrients HMOs. HMOs as prebiotics play a significant role in the development and function of the infant gut microbiota, which in turn affects various aspects of gut development and behavior. The rate of initial brain growth exceeds that of any other organ or body tissue, and by 2 y of age, the brain reaches 80% of its adult weight. Our recent in vivo magnetic resonance spectroscopic (MRS) studies demonstrated that the sialylated HMOs, 3’sialyllactose (3'-SL) and (6'-SL) can alter the level of important brain metabolites and neurotransmitters required for optimal neurodevelopment in piglets. The most abundant nHMO, 2’-fucosyllactose (2'-FL), improved learning and memory in rodent models. However, we do not know if an acidic, neutral or a combination of the two HMOs can act synergistically to provide an enhanced therapeutical role for neurodevelopment, neuroprotection and gut development of newborn.
Effect of human milk oligosaccharides (HMOs) intervention on gut development and behaviour in piglets (2023-2025)
Funding Junlebao Dairy Group Co., LTD, stage one project $613,628
This is the first preclinical study taking a nutraceutical approach to deliver innovative therapeutic applications of key sialylated and neutral or a combination of two human milk oligosaccharides (HMOs) in neurodevelopment, neuroprotection and gut development for newborns. The innovation associated with the assessment of a piglet outcome will allow us to create new knowledge and new insights into the molecular and cellular mechanisms of the therapeutic role of individual HMOs or their combination on brain, gut development, cognitive functions and immunity, with an approach not possible using human subjects.
In 2023 the team successfully completed two piglet’s feeding trials with 32 newborn piglets. More than 12 undergraduate students, 2 PhD students, a research assistant, and staff members participated in this project. All students learned skills including the calculation of daily milk intake, milk preparation, animal feeding, care, animal weighing, cleaning the animal house, and behavioral testing. The team also successfully completed brain MRI scans of all 32 piglets at the Monash Bioimaging Center.