Abstract

Milk fat globule membrane (MFGM) and lactoferrin have been identified as two components that have potential to affect neurodevelopment. While concentrations of some MFGM constituents in infant formulas are within human milk range, they may not be present at optimal or clinically effective levels. However, lactoferrin levels of infant formulas are consistently reported to be lower than human milk. This study sought to provide a novel combination of prebiotics, bovine-derived MFGM, and lactoferrin and assess their influence on neurodevelopment. Twenty-four male piglets were provided either TEST (n = 12) or CONT (n = 12) diet from 2 to 31 days of age. Piglets underwent spatial T-maze assessment starting at 17 days of age, were subjected to magnetic resonance imaging at 30 days of age, and were euthanized for tissue collection at 31 days of age. Diffusion tensor imaging revealed differences in radial (P = 0.032) and mean (P = 0.028) diffusivities in the internal capsule, where CONT piglets had higher rates of diffusion compared with TEST piglets. Voxel-based morphometry indicated larger (P < 0.05) differences in cortical gray and white matter concentrations, with CONT piglets having larger tissue clusters in these regions compared with TEST piglets. In the spatial T-maze assessment, CONT piglets exhibited shorter latency to choice compared with TEST piglets on day 2 of acquisition and days 3 and 4 of reversal. Observed differences in microstructure maturation of the internal capsule and cortical tissue concentrations suggest that piglets provided TEST diet were more advanced developmentally than piglets provided CONT diet. Therefore, supplementation of infant formula with prebiotics, MFGM, and lactoferrin may support neurodevelopment in human infants.

Highlights

  • Life is a period of rapid neurodevelopment and nutrition during this critical phase can have lasting effects on structural and functional neurodevelopment

  • Compositional differences between human milk and infant formulas exist, creating a need to better understand whether specific components in human milk may influence a variety of developmental effects including postnatal brain development

  • The aim of this study was to use the piglet as a pre-clinical model to elucidate potential mechanisms whereby a novel combination of prebiotics, Lf, and milk fat globule membrane (MFGM) affected neurodevelopment beyond what is provided by docosohexaenoic acid (DHA) and arachidonic acid (ARA)

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Summary

Introduction

Life is a period of rapid neurodevelopment and nutrition during this critical phase can have lasting effects on structural and functional neurodevelopment. Breastfeeding is not always a viable option, and it has been recognized that infant formula can substitute for human milk as the sole source of nutrition for infants. Analysis of human and bovine milk revealed lactoferrin (Lf) and milk fat globule membrane (MFGM) as two key components produced throughout lactation [2, 3]. Both Lf and MFGM are comprised of individual compounds that may independently exert beneficial effects on the developing brain, further justifying a need to elucidate their combined actions in early development

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