自闭症谱系障碍（Autism spectrum disorder，ASD）是儿童常见的神经发育障碍性疾病，其发病机制尚不明确。前期我们发现EphB6基因敲除小鼠出现自闭症样行为，同时伴有肠道菌群的紊乱。重要的是，移植EphB6基因敲除小鼠肠道微生物可使C57BL/6J小鼠表现出自闭症样行为，而移植野生型小鼠肠道微生物可改善EphB6基因敲除小鼠的自闭症样行为。功能上EphB6基因敲除小鼠肠道微生物中参与维生素B6代谢通路的基因丰度下降，小鼠血浆和前额叶皮层中维生素B6相对含量下降，而给EphB6基因敲除小鼠补充维生素B6可以改善小鼠受损的社交行为。基于此，我们提出EphB6通过肠道微生物调节维生素B6代谢从而参与小鼠自闭症样行为。本项目拟采用多种小鼠模型明确EphB6通过肠道微生物参与小鼠自闭症样行为的作用及机制。本项目将揭示ASD发生的新机制，并为ASD患者治疗提供潜在的新策略。

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder in children. However, the mechanism of ASD is still not well-characterized. Our pre-experiments found that EphB6 knockout mice displayed autism-like behaviors. Meanwhile, EphB6 knockout mice showed gut dysbacteriosis. Importantly, transplantation of fecal microbiota of EphB6 knockout mice could induce autism-like behaviors in C57BL/6J mice. Also, transplantation of fecal microbiota of wild type mice, which ameliorated gut dysbacteriosis in EphB6 knockout mice, ameliorated the social defects and repetitive behavior of EphB6 knockout mice. Functionally, we found genomic abundance of vitamin B6 metabolism pathway was decreased in fecal microbiota of EphB6 knockout mice. Also, the level of vitamin B6 was decreased in plasma and PFC of EphB6 knockout mice. By injecting vitamin B6 intraperitoneally, EphB6 knockout mice showed an improvement in social behavior. Based on these results, we hypothesized EphB6 modulated autism-like behaviors of mice by gut microbiota, probably by regulating vitamin B6 metabolism. We proposed to prove the role and regulatory mechanism of EphB6 on autism-like behaviors by gut microbiota in mice by using various mouse models. This project will uncover new mechanisms of ASD and provide potential new therapies to treat ASD patients.