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The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism

机译:自闭症的血栓酸大鼠模型与人类自闭症中的肠道细菌脱泻病

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摘要

Abstract Background 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. Methods 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. Results 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. Conclusions 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.
机译:摘要背景肠道菌群有可能影响大脑,这可能反过来影响菌群的组成的常规功能的能力。自闭症谱系障碍(ASD)患者胃肠道问题,并在肠道菌群体验更改吃亏;但是,目前尚不清楚与ASD相关的微生物菌群的变化是否是原因还是疾病的后果。方法我们已经调查了物种的丰富性和微生物组合物在丙戊酸(VPA) - 诱导的大鼠模型孤独症。从直肠粪便样品收集在尸检,微生物总提取DNA,16个rRNA基因利用Illumina测序,和全球微生物共生网络是使用基于理论随机矩阵管道构成。收集老鼠微生物的数据进行了比较,从自闭症的情况下得出的数据。结果我们发现,在怀孕期间VPA管理减少粪便中微生物丰富,改变了肠道微生物组成,并改变了粪便的微生物群落的代谢产物潜力类似于患者ASD看到的模式。然而,全球网络性能和网络组成以及微生物共生模式在很大程度上保存在暴露于VPA的产前管理鼠的后代。结论对自闭症的VPA大鼠模型的微生物我们的数据表明,这种模式,除了行为上和解剖学模仿自闭症患者大脑如前所示,还模仿了微生物自闭症的特点,使之成为最适合的啮齿动物模型中的一个孤独症和自闭症的研究。

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