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

Abstract

Over the last few years, research indicated that Human Milk Oligosaccharides (HMOs) may serve to enhance cognition during development. HMOs hereby provide an exciting avenue in the understanding of the molecular mechanisms that contribute to cognitive development. Therefore, this review aims to summarize the reported observations regarding the effects of HMOs on memory and cognition in rats, mice and piglets. Our main findings illustrate that the administration of fucosylated (single or combined with Lacto-N-neoTetraose (LNnT) and other oligosaccharides) and sialylated HMOs results in marked improvements in spatial memory and an accelerated learning rate in operant tasks. Such beneficial effects of HMOs on cognition already become apparent during infancy, especially when the behavioural tasks are cognitively more demanding. When animals age, its effects become increasingly more apparent in simpler tasks as well. Furthermore, the combination of HMOs with other oligosaccharides yields different effects on memory performance as opposed to single HMO administration. In addition, an enhanced hippocampal long-term potentiation (LTP) response both at a young and at a mature age are reported as well. These results point towards the possibility that HMOs administered either in singular or combination forms have long-lasting, beneficial effects on memory and cognition in mammals.

Clinical Evaluation of 16-Week Supplementation with 5HMO-Mix in Healthy-Term Human Infants to Determine Tolerability, Safety, and Effect on Growth

“…Breast milk contains more than 150 structurally distinct HMOs, which can be divided into three classes: neutral fucosylated, neutral nonfucosylated, and acidic or sialylated HMOs [ 3 ]. HMOs are known to perform a range of beneficial physiological functions including the establishment and maintenance of a healthy gut microbiome [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], the development of the immune system and modulation of inflammatory responses [ 1 , 15 , 16 , 17 ], the strengthening of the gastrointestinal barrier [ 18 , 19 ], and the promotion of neuronal development and cognitive function [ 20 , 21 , 22 , 23 , 24 , 25 ]. These health-promoting effects have been extensively reviewed elsewhere [ 1 , 15 , 26 , 27 ].…”

“…The beneficial functions of HMOs have been shown to depend on the structure of each specific HMO. As an example, sialylated HMOs and 2′-fucosyllactose (2′-FL) have been reported to impact brain development and learning capacities [ 22 , 23 , 25 ], nonfucosylated HMOs are a preferred substrate for specific bifidobacteria [ 8 ], and HMOs from different classes act as decoys to prevent adhesion of specific viral or bacterial pathogens to receptors on human cells [ 28 ]. Navidat et al [ 19 ] recently showed that a blend of six HMOs representing all three classes of HMOs could decrease inflammation-mediated gut barrier disruption by 60%, with 2′-FL being the most effective HMO in the blend.…”

Human milk: From complex tailored nutrition to bioactive impact on child cognition and behavior

“…HMO amount and composition vary between women, are remarkably constant throughout the day and over a week within the same woman but change over the longer course of lactation. How the intake of different HMOs affects immediate and long-term infant health and development, including cognition and behavior, is an active area of research (Docq et al 2020). HMOs may directly interact with infant cells and tissues or/and act indirectly by shaping infant intestinal microbiota (Underwood et al 2015;Totten et al 2012).…”

Comparison of Different Labeling Techniques for the LC-MS Profiling of Human Milk Oligosaccharides

“…Human milk oligosaccharides (HMOs) have been assigned to a variety of important biological functions for infants ( Newburg, 2013 ; Bode, 2015 ; Wicinski et al, 2020 ), such as prevention of pathogens binding to epithelial cell surfaces ( Hester et al, 2013 ; Gonia et al, 2015 ; Triantis et al, 2018 ; Ha et al, 2020 ), functioning as prebiotics ( Boehm et al, 2005 ; Marcobal and Sonnenburg, 2012 ; Underwood et al, 2015 ; Walsh et al, 2020 ), and enhancing brain development ( Oliveros et al, 2018 ; Docq et al, 2020 ; Wu et al, 2020 ). Characterizing the structure(s) and concentration(s) of the isolated specific HMO(s) is essential to elucidate its (or their) molecular mechanisms involved in in vitro studies.…”