Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
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DOI：
10.1016/j.cell.2019.05.004
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发表时间：
2019-05-30
期刊：
影响因子：
64.5
通讯作者：
Mazmanian, Sarkis K.
中科院分区：
文献类型：
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作者：
Sharon, Gil;Cruz, Nikki Jamie;Mazmanian, Sarkis K.
自闭症谱系障碍(ASD)表现为复杂的人类行为的改变，包括社交和刻板印象。除了遗传风险外，典型发育中(TD)和ASD患者的肠道微生物群也不同，尽管目前尚不清楚微生物群是否会导致症状。我们将ASD或TD对照的人类捐赠者的肠道微生物群移植到无菌小鼠中，发现ASD微生物群的定植足以诱导有特征的自闭症行为。被ASD微生物区系定植的小鼠的大脑表现出ASD相关基因的选择性剪接。含有人类微生物区系的小鼠的微生物组和代谢组谱预测，特定的细菌分类群及其代谢产物调节ASD行为。事实上，用候选微生物代谢物治疗ASD小鼠模型可以改善行为异常并调节大脑中的神经元兴奋性。我们认为肠道微生物区系通过产生神经活性代谢物来调节小鼠的行为，这表明肠道-大脑连接在ASD的病理生理学中起到了作用。
Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germfree mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitnhility in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.