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The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism
Molecular Autism ( IF 6.3 ) Pub Date : 2018-12-10 , DOI: 10.1186/s13229-018-0251-3
Fang Liu 1 , Kayla Horton-Sparks 2 , Vanessa Hull 2 , Robert W Li 3 , Verónica Martínez-Cerdeño 2, 4, 5
Affiliation  

Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease. We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism. Fecal samples from the rectum were collected at necropsy, microbial total DNA was extracted, 16 rRNA genes sequenced using Illumina, and the global microbial co-occurrence network was constructed using a random matrix theory-based pipeline. Collected rat microbiome data were compared to available data derived from cases of autism. We found that VPA administration during pregnancy reduced fecal microbial richness, changed the gut microbial composition, and altered the metabolite potential of the fecal microbial community in a pattern similar to that seen in patients with ASD. However, the global network property and network composition as well as microbial co-occurrence patterns were largely preserved in the offspring of rats exposed to prenatal administration of VPA. Our data on the microbiota of the VPA rat model of autism indicate that this model, in addition to behaviorally and anatomically mimicking the autistic brain as previously shown, also mimics the microbiome features of autism, making it one of the best-suited rodent models for the study of autism and ASD.

中文翻译:


丙戊酸自闭症大鼠模型表现出与人类自闭症相似的肠道细菌失调



肠道微生物群能够影响大脑的正常功能,进而影响微生物群的组成。自闭症谱系障碍 (ASD) 患者患有胃肠道问题,肠道菌群发生变化;然而,目前尚不清楚与 ASD 相关的微生物群变化是该疾病的原因还是结果。我们研究了丙戊酸(VPA)诱导的自闭症大鼠模型的物种丰富度和微生物组成。在尸检时收集直肠粪便样本,提取微生物总 DNA,使用 Illumina 对 16 个 rRNA 基因进行测序,并使用基于随机矩阵理论的流程构建全局微生物共现网络。将收集的大鼠微生物组数据与来自自闭症病例的可用数据进行比较。我们发现,怀孕期间服用 VPA 会降低粪便微生物丰富度,改变肠道微生物组成,并改变粪便微生物群落的代谢潜力,其模式与 ASD 患者相似。然而,在产前给予 VPA 的大鼠的后代中,全局网络特性和网络组成以及微生物共现模式在很大程度上得以保留。我们对自闭症 VPA 大鼠模型微生物群的数据表明,该模型除了如之前所示在行为和解剖学上模仿自闭症大脑外,还模仿自闭症的微生物组特征,使其成为最适合自闭症的啮齿动物模型之一。自闭症和自闭症谱系障碍的研究。
更新日期:2018-12-10
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