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

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

doi:10.3389/fnins.2020.00770

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

Front Neurosci. 2020 Aug 13:14:770. doi: 10.3389/fnins.2020.00770. eCollection 2020.

Authors

Stephen A Fleming^{1

2}, Austin T Mudd^{1

2}, Jonas Hauser³, Jian Yan⁴, Sylviane Metairon³, Pascal Steiner³, Sharon M Donovan^{5

6}, Ryan N Dilger^{1

2

5

6}

Affiliations

¹ Piglet Nutrition and Cognition Laboratory, Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States.
² Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, United States.
³ Nestlé Research, Lausanne, Switzerland.
⁴ Nestlé Product Technology Center Nutrition, Vevey, Switzerland.
⁵ Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, United States.
⁶ Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

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.

Keywords: brain; cognition; human milk oligosaccharides (HMOs); milk; neuroimaging; nutrition; pig; prebiotics.