Oral supplementation of 2′-fucosyllactose during lactation improves memory and learning in rats ☆ Elena Oliveros a, ⁎ , María Ramirez a , Enrique Vazquez a , Alejandro Barranco a , Agnes Gruart c , Jose Maria Delgado-Garcia c , Rachael Buck b , Ricardo Rueda a , Maria J. Martin a a Discovery R&D Department, Abbott Nutrition, Granada 18004, Spain b Discovery R&D Department, Abbott Nutrition, Columbus, OH, USA c Division of Neurosciences, Pablo de Olavide University, Seville 41013, Spain Received 17 August 2015; received in revised form 2 December 2015; accepted 21 December 2015 Abstract Human milk oligosaccharides have been proposed to exert beneficial effects on brain development. During the last decades, most of the studies have focused on the evaluation of sialylated structures but recent experiments have also tested fucosylated oligosaccharides, i.e. 2′-fucosyllactose (2′-FL). The present study aimed to determine whether oral 2′-FL has an effect on the development of newborn brain, contributing to enhance cognitive skills later in life. Rat pups received an oral supplementation of 2′-FL (2′-FL group) or water (control group) during the lactation period. Thereafter, animals were maintained on a rodent standard diet. Rats (n =12 rats/group) were evaluated twice, at age 4–6 weeks and again at age 1 year, using classical behavioral tests. In vivo long-term potentiation (LTP) was also performed at the same ages (n = 10 rats/group). Both groups showed similar behavior when the animals were assessed just after weaning (age 4– 6 weeks), although the 2′-FL group seemed to perform slightly better in Morris Water Maze. At age 1 year, 2′-FL rats performed significantly better in the Novel Object Recognition and Y maze paradigms, when compared to controls. In addition, LTP was more intense and longer lasting in the rats supplemented with 2′-FL than in control animals, both in young and adult animals. Oral administration of 2′-FL exclusively during lactation enhanced cognitive abilities, not only in childhood but also in adulthood. © 2016 Elsevier Inc. All rights reserved. Keywords: Milk oligosaccharides; Infant formula; 2′-Fucosyllactose; Cognitive development; Early Nutrition 1. Introduction Breastfeeding is the best feeding choice for a full-term [1] or a preterm newborn [2]. Human milk contains a large number of bioactive compounds that are responsible for its short-term and long-term health benefits on immunity, growth or development. Thus, it has been demonstrated that breastfed infants develop diarrhea [3], food allergies [4], autoimmune diseases [5] or metabolic syndrome [6] to a lesser extent when compared with formula-fed infants. Many studies also report that breastfeeding is associated with higher intelligence quotient (IQ) scores, either at school ages or during adulthood [7]. Oligosaccharides are postulated as one of those functional components, representing the third largest fraction of breast milk. A differential feature of oligosaccharides is the ability to resist digestion allowing them to play a significant role in the development of the newborn immune system of the newborn [8], not only by preventing the adhesion of pathogens to epithelial cell surfaces [9–11] but also by acting as bifidogenic substrates in the lower gastrointestinal tract [12,13]. The amount of human milk oligosaccharides (HMOs) widely varies among women and over the lactation period [14] from 20 to 25 g/L in colostrum to 12–15 g/L in mature milk [15]. The basic oligosaccharide structure includes a lactose unit that can be elongated at the reducing end by N-acetyllactosamine units. The structural diversity is due to an extensive fucosylation and/or sialylation with fucose and sialic acid residues added at the terminal positions [16,17]. Taking this last point into account, a general classification of HMOs distinguishes two different groups: neutral oligosaccharides and acidic oligosaccharides mainly composed of sialylated structures [18]. Neutral oligosaccharides include fucosylated molecules. Fucosy- lated oligosaccharide content of individual milk depends on a woman's histoblood group according to the Lewis and Secretor systems. Secretor mothers (Se + ) represent 85% of the population and their milk contains one of the most predominant fucosylated oligosaccharide, 2′-fucosyllactose (2′-FL) [19].2′-FL is a major oligosaccharide in human milk [20] reaching a concentration of 3.93 ± 1.11 g/L in colostrum. It has been reported that there is a 2′-FL range of 0.06–4.85 g/L in mature milk [21] and, thereafter, its level declines to 1.2 g/L at 1 year postpartum [22].2′-FL is not only present Available online at www.sciencedirect.com ScienceDirect Journal of Nutritional Biochemistry 31 (2016) 20 – 27 ☆ There is no funding to be disclosed. ⁎ Corresponding author. R&D Department, Abbott Laboratories, Camino de Purchil, 64, 18004 Granada, Spain. Tel.: + 34-958249822. E-mail address: elena.oliveros@abbott.com (E. Oliveros). http://dx.doi.org/10.1016/j.jnutbio.2015.12.014 0955-2863/© 2016 Elsevier Inc. All rights reserved.