Qi Zhaoyao, Lyu Mengke, Yang Liping, Yuan Haiyan, Cao Yun, Zhai Linlin, Dang Weili, Liu Juan, Yang Fan, Li Ying
Basic Medical College, Henan University of Chinese Medicine, Zhengzhou, China.
Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China.
Front Psychiatry. 2021 Mar 12;12:549810. doi: 10.3389/fpsyt.2021.549810. eCollection 2021.
Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model. We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA). First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of and , recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of and increased (), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation. Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD. The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，目前缺乏能够重现ASD疾病状态的理想动物模型。以往研究报道，将ASD患者的肠道微生物群移植到怀孕小鼠体内足以促使其后代出现类似自闭症的行为变化。本研究旨在探讨粪便微生物群移植（FMT）是否可作为建立ASD动物模型的新方法。我们将ASD儿童的粪便样本提取物反复移植到怀孕大鼠体内（rFMT），以建立ASD大鼠模型（oFMT），并将其与经典的丙戊酸（VPA）模型（oVPA）进行比较。首先，我们发现oFMT表现出发育迟缓及ASD的典型行为特征，这与之前的研究一致。其次，oFMT的肠道微生物群主要由[具体微生物名称1]和[具体微生物名称2]组成，重现了ASD患者肠道微生物群的异常情况。在oFMT中，[具体微生物名称1]和[具体微生物名称2]的丰度增加（[具体数值]），与oVPA相比，肠道微生物群也表现出高度一致性。第三，oFMT血清中5-羟色胺（5-HT）的表达增加，oFMT血清中的γ-氨基丁酸（GABA）和去甲肾上腺素（NE）减少。第四，oFMT的肠道微生物群还具有一些在oVPA中未发现的ASD特征性肠道微生物。第五，用VPA处理的怀孕大鼠表现出显著的免疫激活，而接受FMT的大鼠免疫激活相对较轻。尽管建立FMT自闭症大鼠模型（oFMT）的机制尚未明确，但数据表明该模型具有较高的结构效度，FMT模型很可能是一种新的、可靠的潜在ASD动物模型，并且在研究ASD的肠道微生物群方面将具有潜在价值。FMT自闭症大鼠模型具有较高的结构效度，FMT模型很可能是一种新的、可靠的潜在ASD动物模型。
