Department of Biomedicine and Prevention, Section of Clinical Nutrition and Nutrigenomic, University of Roma "Tor Vergata", Rome, Italy; Health Center srl, Via Sabotino 56, 87100 Cosenza, Italy; Laboratory of Comparative Neuroanatomy, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, Cosenza, Italy.
Laboratory of Comparative Neuroanatomy, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, Cosenza, Italy.
Neuroscience. 2022 Aug 21;498:174-189. doi: 10.1016/j.neuroscience.2022.06.038. Epub 2022 Jul 2.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder displaying the modification of complex human behaviors, characterized by social interaction impairments, stereotypical/repetitive activities and emotional dysregulation. In this study, fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to valproic acid (VPA). Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p < 0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice as compared to controls. Indeed altered behaviors of FMT mice was reported when evaluated in the different maze tests (light dark, novel object, three chamber tests, novel cage test). Contextually, FMT accounted for elevated expression levels of the pro-inflammatory factors IL-1β, IL-6, COX-1 and TNF-α in both brain and small intestine. Villous atrophy and inflammatory infiltration (Caspase 3 and Ki67) were increased in the small intestine of FMT and VPA mice compared to controls. Moreover, the observed FMT-dependent alterations were linked to a decrease in the methylation status. Overall, findings of the present study corroborate a key role of gut microbiota in ASD. However, further investigations are required before any possible manipulation of gut bacteria with appropriate diets or probiotics can be conducted in ASD individuals.
自闭症谱系障碍（ASD）是一种神经发育障碍，表现为复杂人类行为的改变，其特征是社交互动障碍、刻板/重复活动和情绪失调。在这项研究中，通过灌胃将自闭症儿童供体的粪便微生物群移植（FMT）到小鼠体内，与暴露于丙戊酸（VPA）的孕鼠的后代相比，导致了类似于 ASD 的微生物群和自闭症行为的定植。与对照组相比，这种变化似乎与厚壁菌门的增加以及放线菌和 Candidatus S.的显著减少（p<0.001）密切相关。事实上，当在不同的迷宫测试（明暗、新物体、三箱测试、新笼测试）中评估 FMT 小鼠的行为时，发现了改变。在大脑和小肠中，FMT 导致促炎因子 IL-1β、IL-6、COX-1 和 TNF-α的表达水平升高。与对照组相比，FMT 和 VPA 小鼠的小肠绒毛萎缩和炎症浸润（Caspase 3 和 Ki67）增加。此外，观察到的 FMT 依赖性改变与甲基化状态的降低有关。总的来说，本研究的结果证实了肠道微生物群在 ASD 中的关键作用。然而，在 ASD 个体中进行适当饮食或益生菌对肠道细菌的可能操纵之前，还需要进一步的研究。
