Human and Bovine Milk Oligosaccharides Elicit Improved Recognition Memory Concurrent With Alterations in Regional Brain Volumes and Hippocampal mRNA Expression.

Pascal Steiner,Jonas Hauser,Stephen A Fleming,Sylviane Metairon,Jian Yan,Austin T Mudd,Ryan N Dilger,Sharon M Donovan

doi:10.3389/fnins.2020.00770

Abstract

Human milk contains a unique profile of oligosaccharides (OS) and preliminary evidence suggests they impact brain development. The objective of this study was to assess the impact of bovine and/or human milk oligosaccharides (HMO) (2′-fucosyllactose and Lacto-N-neotetraose) on cognition, brain development, and hippocampal gene expression. Beginning on postnatal day (PND) 2, male pigs received one of four milk replacers containing bovine milk oligosaccharides (BMOS), HMO, both (BMOS + HMO), or neither. Pigs were tested on the novel object recognition task using delays of 1- or 48-h at PND 22. At PND 32–33, magnetic resonance imaging procedures were used to assess structural brain development and hippocampal tissue was collected for analysis of mRNA expression. Pigs consuming only HMO exhibited recognition memory after a 1-h delay and those consuming BMOS + HMO exhibited recognition memory after a 48-h delay. Both absolute and relative volumes of cortical and subcortical brain regions were altered by diet. Hippocampal mRNA expression of GABRB2, SLC1A7, CHRM3, and GLRA4 were most strongly affected by diet. HMO and BMOS had distinct effects on brain structure and cognitive performance. These data suggest different mechanisms underlie their influence on brain development.

Highlights

Human milk oligosaccharides (HMO) are increasingly recognized as important promoters of intestinal and immune development (Kirmiz et al, 2018)
Emerging research has suggested that bovine milk derived oligosaccharides (BMOS) and human milk oligosaccharides (HMO) [e.g., 2 -fucosyllactose (2 FL), Lacto-N-neotetraose (LNnT)] may confer physiological benefits when consumed by formula-fed infants
Rats supplemented with 2 -FL demonstrated vagally mediated improved learning and memory (Vázquez et al, 2015, 2016; Oliveros et al, 2016), rats supplemented with sialyllactose demonstrated improved behavioral response to stress (Tarr et al, 2015), and we have demonstrated that pigs fed a combination of polydextrose and GOS (Fleming et al, 2017) have improved performance in the novel object recognition (NOR) task

Summary

Introduction

Human milk oligosaccharides (HMO) are increasingly recognized as important promoters of intestinal and immune development (Kirmiz et al, 2018). Emerging research has suggested that bovine milk derived oligosaccharides (BMOS) and HMO [e.g., 2 -fucosyllactose (2 FL), Lacto-N-neotetraose (LNnT)] may confer physiological benefits when consumed by formula-fed infants. Infants fed formula supplemented with BMOS have shown tolerance and adequate growth as measured by anthropomorphic measures (e.g., weight-for-age, lengthfor-age, or head-circumference scores) and stool characteristic (e.g., frequency, consistency, or pH) closer to that of breastfed infants (Meli et al, 2014; Cooper et al, 2016; Simeoni et al, 2016; Radke et al, 2017). Lactis brought fecal bifidobacteria counts of infants delivered via C-section closer to that of infants delivered vaginally (Cooper et al, 2016), and the same combination brought 16S ribosomal RNA sequencing indices of richness, evenness, and the Shannon index similar to that of a breastfed control group

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