Fang Jingjing, 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.
Nutrients. 2025 Jan 10;17(2):247. doi: 10.3390/nu17020247.
BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impaired social interaction and repetitive stereotyped behavior. Effective interventions for the core autistic symptoms are currently limited.
This study employed a valproic acid (VPA)-induced mouse model of ASD to assess the preventative effects of L-proline supplementation on ASD-like behaviors. The method of 16S rRNA sequencing and untargeted metabolomics analyses were conducted to investigate the modulation of gut microbiota and gut metabolites by L-proline.
The results indicated that L-proline supplementation significantly prevented ASD-like behavioral disorders, including alleviating social communication deficits and reducing repetitive behavior in the ASD mice. The 16S rRNA sequencing analysis revealed that L-proline regulated the composition and structure of gut microbiota. L-Proline supplementation enhances the abundance of the at the phylum level and the at the genus level, while concurrently reducing the abundance of the at the phylum level, as well as the , , and at the genus level in the VPA-induced mouse model for ASD. Additionally, the untargeted metabolomics results indicated that L-proline also modified the gut metabolite profiles. Functional analysis of the gut microbiota and KEGG pathway enrichment analysis of differential metabolites between the L-proline-supplemented and VPA groups corroborated that L-proline decreased pathways related to nucleotide metabolism, taurine and hypotaurine metabolism, and pyruvate metabolism, while increasing pathways involved in alpha-linolenic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. The integrative metabolomic and microbiome analyses showed strong connections between the gut metabolites and gut microbiota affected by L-proline. These findings suggest that the modulatory effects of L-proline on gut microbiota and its metabolites may play a crucial role in preventing autism in mice.
These findings suggest that dietary L-proline may represent a viable, effective option for preventing the physiological and behavioral deficits associated with ASD in mice.
背景/目的：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。
本研究采用丙戊酸（VPA）诱导的ASD小鼠模型，评估补充L-脯氨酸对ASD样行为的预防作用。采用16S rRNA测序和非靶向代谢组学分析方法，研究L-脯氨酸对肠道微生物群和肠道代谢产物的调节作用。
结果表明，补充L-脯氨酸可显著预防ASD样行为障碍，包括减轻ASD小鼠的社交沟通缺陷和减少重复行为。16S rRNA测序分析显示，L-脯氨酸调节肠道微生物群的组成和结构。在VPA诱导的ASD小鼠模型中，补充L-脯氨酸可提高门水平上的 丰度和属水平上的 丰度，同时降低门水平上的 丰度以及属水平上的 、 和 丰度。此外，非靶向代谢组学结果表明，L-脯氨酸还改变了肠道代谢产物谱。对补充L-脯氨酸组和VPA组之间的肠道微生物群进行功能分析以及对差异代谢产物进行KEGG通路富集分析证实，L-脯氨酸减少了与核苷酸代谢、牛磺酸和亚牛磺酸代谢以及丙酮酸代谢相关的通路，同时增加了与α-亚麻酸代谢以及苯丙氨酸、酪氨酸和色氨酸生物合成相关的通路。代谢组学和微生物组的综合分析表明，L-脯氨酸影响的肠道代谢产物与肠道微生物群之间存在紧密联系。这些发现表明，L-脯氨酸对肠道微生物群及其代谢产物的调节作用可能在预防小鼠自闭症中起关键作用。
这些发现表明，饮食中的L-脯氨酸可能是预防小鼠ASD相关生理和行为缺陷的一种可行、有效的选择。
