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Published on: June 2, 2022
Neonatal 2'-Fucosyllactose Supplementation Modulates Exploratory Behavior and Hippocampal Synaptic Plasticity in Rats
Miao Yu1,2, Jin Wang1,2, Ruixin Kou1,2
1Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.
Abstract:
2'-Fucosyllactose (2'-FL) represents a significant constituent within human milk oligosaccharides, and its benefits for intestinal health and neurodevelopment in infants and young children have been widely recognized. However, the mechanism by which 2'-FL influences early-life behavioral development through the gut-brain axis remains incompletely understood. In this study, we investigated the effects of neonatal 2'-FL supplementation on behavioral development in Sprague-Dawley (SD) rats and explored its potential microbiota-metabolite regulatory mechanisms. After 4 consecutive weeks of oral gavage beginning on postnatal day 2, rats receiving 2'-FL showed significantly increased average movement speed and central-area exploration time in the open field test. From a systemic perspective, 2'-FL lowered blood diamine oxidase (DAO) and D-lactic acid (D-LA) concentrations while elevating colonic mRNA levels of tight junction protein-related genes, consequently enhancing intestinal barrier stability. In addition, 16S rRNA sequencing showed that 2'-FL reshaped the gut microbiota structure and significantly enriched Lactobacillus, Bacteroides, and short-chain fatty acid (SCFA)-associated taxa represented by Lachnospiraceae_NK4A136_group. Untargeted metabolomics revealed that 2'-FL induced systemic metabolic remodeling, characterized by upregulation of the bioactive metabolites dehydroepiandrosterone sulfate (DHEA-S) and deoxycholic acid (DCA), and downregulation of the glucocorticoid-related corticosterone. Western blot validation further showed higher hippocampal protein expression of postsynaptic density protein 95 (PSD95), brain-derived neurotrophic factor (BDNF), and synaptophysin in the 2'-FL group, supporting enhanced synaptic plasticity-related signaling. In summary, neonatal 2'-FL intervention enhanced exploratory behavior and was accompanied by increased hippocampal synaptic plasticity-related protein expression in rats, potentially through coordinated regulation of gut microbiota composition and systemic metabolism.
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