Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.-猫眼课题宝

DOI：

10.1016/j.cell.2013.11.024

发表时间：

2013-12-19

期刊：

Cell

影响因子：

64.5

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Hsiao EY;McBride SW;Hsien S;Sharon G;Hyde ER;McCue T;Codelli JA;Chow J;Reisman SE;Petrosino JF;Patterson PH;Mazmanian SK

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897394/?report=classic

虽然自闭症谱系障碍（ASD）是由核心行为障碍定义的，但胃肠道（GI）症状也是常见的。ASD个体的亚群显示肠道微生物群的生态失调，并且一些表现出增加的肠道通透性。在这里，我们展示了GI屏障缺陷和微生物群改变的小鼠模型显示ASD的特征，母体免疫激活（MIA）。口服治疗MIA后代与人类肠道脆弱拟杆菌纠正肠道通透性，改变微生物组成，并改善ASD相关的缺陷，沟通，刻板，焦虑样和感觉运动行为。MIA后代显示改变的血清代谢组学特征，和B。fragilis调节几种代谢物的水平。用MIA增加并由B恢复的代谢物处理未处理小鼠。fragilis会导致行为异常，这表明肠道细菌对宿主代谢组的影响会影响行为。总之，这些发现支持ASD中的肠道-微生物组-大脑联系，并确定了自闭症GI和行为症状的潜在益生菌疗法。

Although autism spectrum disorder (ASD) is defined by core behavioral impairments, gastrointestinal (GI) symptoms are commonly reported. Subsets of ASD individuals display dysbiosis of the gut microbiota, and some exhibit increased intestinal permeability. Here we demonstrate GI barrier defects and microbiota alterations in a mouse model displaying features of ASD, maternal immune activation (MIA). Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition and ameliorates ASD-related defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naïve mice with a metabolite that is increased by MIA and restored by B. fragilis causes behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in ASD and identify a potential probiotic therapy for GI and behavioral symptoms of autism.