Cognitive and behavioral benefits of 2′-fucosyllactose in growing mice: the roles of 5-hydroxytryptophan and gut microbiota

作者：Liuying Zhu, Zhiyi Zhang, Ting Luo, Hongyan Li, Zeyuan Deng, Jing Li, Liufeng Zheng, Jinqiang Liao, Minghui Wang, Bing Zhang · 发表于：Microbiome · 年份：2025 · DOI：10.1186/s40168-025-02094-x · 被引用次数：20 · 研究领域：Infant Nutrition and Health、Gut microbiota and health、Gastrointestinal motility and disorders

BACKGROUND: 2'-Fucosyllactose (2'-FL) is one of the major oligosaccharides found in human breast milk, with several recognized beneficial effects on the host. Extensive research has indicated positive effects of 2'-FL on cognitive development in the brain, yet its molecular mechanisms have remained elusive. This study aimed to assess the impact of 2'-FL on the gut-brain axis microbiota and cognitive function in growing mice, along with its potential mechanisms of action. RESULTS: Following long-term supplementation for 4 weeks, 2'-FL was found to enhance cognitive memory function in growing mice (3 weeks old) as assessed through Y-maze, novel object recognition, and water maze tests. Analysis via 16S rRNA sequencing revealed significant alterations in gut microbiota diversity and composition induced by 2'-FL, notably increasing the relative abundance of Bacteroides and Lactobacillus genera. Additionally, 2'-FL significantly elevated levels of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) in the hippocampal tissue. However, antibiotic intervention abolished the cognitive advantage conferred by 2'-FL, highlighting the critical role of gut microbiota in mediating its effects. Similarly, short-term supplementation with 2'-FL for 7 days indicated rapid changes in gut microbiota composition preceding cognitive improvements, further suggesting a potential causal relationship between gut microbiota characteristics and cognition. Further, in vitro experiments with mouse f...