Fang Jingjing, Guo Jingya, Lao Yujie, Kang Seong-Gook, Huang Kunlun, Tong Tao
Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Department of Food Engineering and Solar Salt Research Center, Mokpo National University, Muangun 58554, Republic of Korea.
Brain Behav Immun. 2025 Jul;127:358-374. doi: 10.1016/j.bbi.2025.03.025. Epub 2025 Mar 20.
Autism spectrum disorder (ASD) is characterized by impaired social interaction and repetitive stereotyped behavior, and effective interventions for the core autistic symptoms are currently limited. This study examines the protective role of L-tyrosine in alleviating ASD-like behavioral disorders in a valproic acid (VPA)-induced ASD mouse model and explores the underlying mechanisms via integrated multi-omics. We first investigated the potential of dietary L-tyrosine in mitigating autistic behavior. Subsequently, 16S rRNA sequencing, hippocampal transcriptomics, and neurotransmitter metabolome were employed to elucidate the underlying mechanism. Further, we conducted transplantation of the L-tyrosine-regulated microbiota in VPA-induced ASD mice. The results showed that L-tyrosine supplementation significantly mitigates ASD-like behavioral disorders, alleviates social communication deficits, and reduces repetitive behavior in autistic mice. L-tyrosine also attenuates the neuronal loss caused by VPA treatment in the DG and CA1 hippocampal regions in mice. The hippocampi of the L-tyrosine-treated mouse model for ASD displays modified gene expression profiles and different neurotransmitter levels. L-tyrosine also mitigates colonic barrier damage and amends the gut microbial composition and function. The integrative transcriptomic, metabolomic, and microbiome analysis shows strong connections between the hippocampal genes, neurotransmitters, and gut microbiota affected by L-tyrosine. The transplantation of microbiota from L-tyrosine-treated mice to VPA-induced ASD mice recipients recapitulated the preventive and protective effects of L-tyrosine on autistic behavior disorders. These findings suggest that dietary L-tyrosine may represent a viable, effective treatment option for managing the physiological and behavioral deficits associated with ASD.
自闭症谱系障碍（ASD）的特征是社交互动受损和重复刻板行为，目前针对自闭症核心症状的有效干预措施有限。本研究探讨了L-酪氨酸在减轻丙戊酸（VPA）诱导的ASD小鼠模型中ASD样行为障碍方面的保护作用，并通过综合多组学方法探索其潜在机制。我们首先研究了饮食中L-酪氨酸减轻自闭症行为的潜力。随后，采用16S rRNA测序、海马转录组学和神经递质代谢组学来阐明潜在机制。此外，我们对VPA诱导的ASD小鼠进行了L-酪氨酸调节的微生物群移植。结果表明，补充L-酪氨酸可显著减轻自闭症小鼠的ASD样行为障碍，缓解社交沟通缺陷，并减少重复行为。L-酪氨酸还可减轻VPA处理导致的小鼠海马齿状回（DG）和海马体CA1区的神经元损失。L-酪氨酸处理的ASD小鼠模型的海马体显示出基因表达谱和神经递质水平的改变。L-酪氨酸还可减轻结肠屏障损伤，并改善肠道微生物组成和功能。综合转录组学、代谢组学和微生物组分析表明，L-酪氨酸影响的海马基因、神经递质和肠道微生物群之间存在紧密联系。将L-酪氨酸处理小鼠的微生物群移植到VPA诱导的ASD小鼠受体中，重现了L-酪氨酸对自闭症行为障碍的预防和保护作用。这些发现表明，饮食中的L-酪氨酸可能是管理与ASD相关的生理和行为缺陷的一种可行、有效的治疗选择。
