Supplementation of 2′-Fucosyllactose during the Growth Period Improves Neurodevelopmental Disorders in Offspring Mice Induced by Maternal Immune Activation
Xiaoning Wu, Tengzheng Cao, Jin Ye, Renjie Shi, Xiaowei Bao, Yongjie Ge, Dongning Li, Shijin Hao, Feitong Liu, Xuebo Liu
Abstract
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.