Early-life 2′-fucosyllactose and its combination with Bifidobacterium bifidum TMC3115: Sex-specific effects in learning, spatial memory, and hyperactivity in juvenile spontaneous hypertensive rats as an attention deficit/hyperactivity disorder model

This study investigated the preventive effects of early-life intervention with 2'-fucosyllactose (2'-FL) or synbiotic (2'-FL plus Bifidobacterium bifidum TMC3115) on newborn spontaneous hypertensive rats (SHR) as an attention deficit/hyperactivity disorder (ADHD) model, focusing on the microbiota-gut-brain (MGB) axis. In male SHR, 2'-FL intervention increased time spent and distance moved in Morris water maze, and upregulated mRNA expression related to γ-aminobutyric acidergic, serotonergic, and noradrenergic systems in hippocampus. Increased Romboutsia, Clostridium_sensu_stricto_1, and decreased Muribaculaceae after 2'-FL intervention were associated with improved learning and spatial memory. In female SHR, synbiotic intervention reduced hyperactivity in the open field test and increased expression of tyrosine hydroxylase and dopamine transporter in striatum. Synbiotic also promoted gut microbiota diversity and suppressed the growth of Bacillus and Turicibacter. Overall, early-life 2'-FL and synbiotic interventions offered sex-specific benefits for SHR by regulating gut microbiota and mediating MGB pathways, providing new insights for prebiotics and psychobiotics in early ADHD prevention.