荷兰乌得勒支大学Paula Perez-Pardo研究团队发现，益生元饮食可使自闭症谱系障碍小鼠模型中的异常免疫和行为表型恢复正常。2024年4月8日，《中国药理学报》在线发表了这项成果。

研究人员探讨了含有特定益生纤维（即3%的半乳寡糖/果寡糖（GOS/FOS; 9:1））的饮食，是否能减轻小鼠子宫内暴露于丙戊酸（VPA）的不良影响。怀孕的BALB/cByJ母鼠在妊娠第11天（G11）注射VPA（600毫克/千克，皮下注射）或磷酸盐缓冲盐水（PBS）。雄性后代分为四组：(1)宫内PBS 暴露与对照饮食组；(2)宫内PBS暴露与GOS/FOS饮食组；(3)宫内VPA暴露与对照饮食组；(4)宫内VPA暴露与GOS/FOS饮食组。饮食干预从出生开始，并持续整个实验过程。

研究表明，益生元饮食能使VPA诱导的雄性后代的改变正常化，包括恢复关键微生物类群、肠道通透性、外周免疫稳态、减少小脑的神经炎症以及小鼠的社交行为和认知障碍。总之，这项研究为了解肠脑轴在自闭症谱系障碍（ASD）发展中的参与提供了宝贵的见解。此外，饮食干预可能会纠正肠道微生物群和免疫反应的失衡，并最终改善ASD的有害行为结果。

据了解，ASD是一组以沟通和行为障碍为特征的神经发育障碍。越来越多的证据表明，微生物群-肠道-大脑轴以及可能与之相关的免疫失衡可能在这种疾病的发展中起着一定的作用。胃肠道缺陷和肠道微生物群功能紊乱与ASD行为的发展或严重程度有关。因此，针对特定饮食的治疗可能会改善ASD患者的胃肠功能和异常行为。

附：英文原文

Title: Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder

Author: Prince, Naika, Peralta Marzal, Lucia N, Markidi, Anastasia, Ahmed, Sabbir, Adolfs, Youri, Pasterkamp, R Jeroen, Kumar, Himanshu, Roeselers, Guus, Garssen, Johan, Kraneveld, Aletta D, Perez-Pardo, Paula

Issue&Volume: 2024-04-08

Abstract: Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.

DOI: 10.1038/s41401-024-01268-x

Source: https://www.nature.com/articles/s41401-024-01268-x