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

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.

The Protective and Long-Lasting Effects of Human Milk Oligosaccharides on Cognition in Mammals

“…In the piglet studies, different retention intervals, ranging from 1 h (intermediate) to 48 h (long-term), were used. It is possible that similar enhancing effects of HMO administration on recognition memory (NORT) reported by Fleming and colleagues [52,53] would have been found in juvenile rodents if the retention interval was 1 h instead of 24 h and if the rodents had been fed a similar combination of oligosaccharides as the piglets received. However, when probing such a long-term recognition memory of one-year old rodents, an improved recognition memory is observed in the HMO supplemented animals, together with improved spatial memory as measured by the Y maze.…”

“…When rodents performed spatial and recognition memory tests during adolescence and early adulthood, no effects of either fucosylated or sialylated HMOs, as assessed by the NORT (when tested 24 h after the acquisition phase), MWM and the Y maze, were reported. Contrary to the rodent studies, three piglet studies showed that supplementing HMOs during the lactation period resulted in improved spatial memory (T maze) in infancy [51] and object recognition (NORT) [52,53]. Supplementing only oligofructose or the combination of 2 FL and LNnT increased object recognition when piglets were tested one hour after the acquisition phase.…”

“…Supplementing mammals with additional HMOs leads to beneficial cognitive outcomes under certain specific circumstances (Table 1, Figure 2). In general, both fucosylated and sialylated HMOs contribute to an improved memory performance and faster learning speed (tests described in Figure 1A-G) when tested in mature adulthood, irrespective of the age of administration of these HMOs (e.g., during infancy or adulthood) [46][47][48][49][50][51][52][53][54]. , animal model (rodents versus piglets) and the age of when the behavioural test has been performed.…”

“…Supplementing only oligofructose or the combination of 2 FL and LNnT increased object recognition when piglets were tested one hour after the acquisition phase. When tested 48 h later, only the piglets who received a combination of either Bovine Milk Oligosaccharides (mostly neutral non fucosylated oligosaccharides) and 2 FL and LNnT [52] or Oligofructose and 2 -FL [53] displayed long-term recognition memory. In mature adulthood (older than 1 year), rodent studies also found significant differences in both the Y maze and the NORT for both sialylated and fucosylated HMOs.…”

“…In this study, they found no differences between the sialyllactose group and control group on the NORT performed during infancy. Fleming et al, 2020a [52] Pigs (1050 Cambro genetics)…”