Dietary Prebiotics, Milk Fat Globule Membrane, and Lactoferrin Affects Structural Neurodevelopment in the Young Piglet

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: brain; internal capsule; lactoferrin; milk fat globule membrane; neurodevelopment; nutrition; pig; prebiotics.

Figure 1

Spatial T-maze behavioral assessment revealed differences due to diet in latency to choice, on three separate days. (A) Behavior performance was assessed by proportion of correct choices, out of 10 trials, per day. No differences were observed between dietary treatments. (B) Analysis of latency to choice revealed differences (P < 0.05) on day 2 of acquisition and days 3 and 4 of reversal, in all cases TEST piglets exhibited longer latencies compared with CONT piglets on these days.

Figure 2

Voxel-based morphometry heat maps illustrating tissue concentration differences between TEST- and CONT-fed piglets. The color bar indicates pseudo-t statistics, used to determine the P-uncorrected statistics listed in Table 1. (A) Gray matter tissue differences in which CONT piglets have more gray matter than TEST piglets. (B) Gray matter tissue differences in which TEST piglets have more gray matter than CONT piglets. (C) White matter tissue differences in which CONT piglets have more white matter than TEST piglets. Illustration for white matter differences where TEST piglets have more white matter than CONT, not shown.

Figure 3

Radial and mean diffusivity indicate greater maturation in the internal capsule of TEST-fed piglets compared with CONT. (A) Radial diffusivity measures revealed CONT piglets had higher (P = 0.032) rates of diffusion compared with TEST piglets. (B) Mean diffusivity measures revealed CONT piglets had higher (P = 0.028) rates of diffusion compared with TEST piglets. * denotes significant (P < 0.05) difference between TEST and CONT piglets.