Supplementation of 2′-Fucosyllactose during the Growth Period Improves Neurodevelopmental Disorders in Offspring Mice Induced by Maternal Immune Activation

Autism spectrum disorder is a serious neurodevelopmental disorder whose early onset significantly affects an individual’s social interactions and cognitive function. Recent research suggests that modulating the gut microbiota could be a potential intervention strategy for autism spectrum disorder symptoms. 2′-Fucosyllactose has been identified as a regulator of gut microbiota homeostasis, however, its effectiveness in addressing autism spectrum disorder remains unclear. In this study, the effects of daily supplementation of 2′-FL in 3-week-old male offspring mice for 5 weeks were examined. The results showed that 2′-fucosyllactose significantly improved autism spectrum disorder-like behavioral deficits. Furthermore, supplementation with 2′-fucosyllactose restored intestinal barrier integrity and increased relative abundance of beneficial gut bacteria, particularly Akkermansia and Bifidobacterium that are closely related to bile acid metabolism. Notably, 2′-fucosyllactose treatment elevated the content of bile acids and upregulated the expression of bile acid receptors in the brain. Co-housing experiments further confirmed the crucial role of gut microbiota in mediating the beneficial effects of 2′-fucosyllactose. Overall, this study suggests that 2′-fucosyllactose could alleviate maternal immune activation-induced behavioral deficits and neuroinflammation through the regulation of the gut–brain axis, offering potential therapeutic value.