Early-life supplementation with 2'-FL promotes the structural and functional integrity of the brain in mice at weaning and adolescence.

2'-fucosyllactose (2'-FL) was found to improve cognitive function and was approved for use in infant formula. Given that brain maturation continues through adolescence and even into adulthood, the extent of 2'-FL's cognitive benefits remains to be evaluated. This study administered 2'-FL to mice from 4 to 42 days of age and evaluated its benefits on structural and functional development following LPS challenge. Both 0.5 and 2 mg/g body weight/day 2'-FL significantly upregulated genes related to neurodevelopment (NGF, BDNF), myelination (MBP, Olig2), and synaptic function (PSD95, Synaptophysin, Drebrin) at weaning. Mice daily supplemented with 2 mg 2'-FL significantly resisted LPS-induced cognitive and neuronal damage, glial overactivation, and associated neuroinflammation at adolescence (42 days), indicating enhanced brain maturation. Furthermore, 2'-FL elevated intestinal contents and serum levels of PS (16:0/18:1) while reducing prostaglandin E2. These changes in metabolite abundance are associated with promoting the development of brain structure and function. This study laid the foundation for applying 2'-FL in milk powders besides infant formula with brain development claims.