Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder.
Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder.
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DOI：
10.1038/srep45356
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发表时间：
2017-03-28
影响因子：
4.6
通讯作者：
Lembo F
中科院分区：
文献类型：
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作者：
Coretti L;Cristiano C;Florio E;Scala G;Lama A;Keller S;Cuomo M;Russo R;Pero R;Paciello O;Mattace Raso G;Meli R;Cocozza S;Calignano A;Chiariotti L;Lembo F
微生物-肠-脑轴的改变在自闭症谱系障碍（ASD）的发病机制中被引用。小鼠模型可能是了解肠道生态失调和相关改变如何导致自闭症表型的一个很好的工具。在这项研究中，我们对BTBR T + tf/J （BTBR）近交系小鼠（ASD动物模型）的肠道微生物群（GM）特征、行为特征、肠道完整性和结肠组织免疫学特征进行了比较。性别差异，迄今为止很少研究动物模型，具体解决。结果表明，亲社会的C57BL/6j （C57）菌株对两性BTBR小鼠均表现出明显的肠道生态失调、行为改变、肠道通透性改变和免疫状态改变。值得注意的是，性别相关的差异被清楚地发现了。我们发现拟杆菌、拟副杆菌、Sutterella、去盐杆菌和Oscillospira属是与选择的病理特征相关的性别特异性肠道微生物群特征的关键驱动因素。综上所述，我们的研究结果表明，BTBR小鼠的转基因改变显示出相关的性别相关差异，并支持使用BTBR小鼠模型来解剖自闭症相关的微生物-肠-脑轴改变。
Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.