Institute of Endocrinologia ed Oncologia Sperimentale, IEOS, Consiglio Nazionale delle Ricerche CNR, Via S. Pansini, 5, 80131, Naples, Italy.
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
Sci Rep. 2017 Mar 28;7:45356. doi: 10.1038/srep45356.
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.
微生物群-肠道-大脑轴的改变已被认为与自闭症谱系障碍（ASD）的发病机制有关。小鼠模型可以代表一种极好的工具，可以了解肠道菌群失调和相关改变如何导致自闭症表型。在这项研究中，我们平行研究了自闭症模型 BTBR T ⁇ + tf/J（BTBR）近交系小鼠的肠道微生物群（GM）谱、行为特征、肠道完整性和结肠组织的免疫学特征。特别针对目前在动物模型中研究甚少的性别差异进行了研究。结果表明，与亲社会的 C57BL/6j（C57）品系相比，雌雄 BTBR 小鼠均表现出明显的肠道菌群失调、行为改变、肠道通透性和免疫状态改变。值得注意的是，明显检测到了与性别相关的差异。我们确定了拟杆菌属、副拟杆菌属、萨特氏菌属、脱硫杆菌属和颤螺菌属作为与选定病理特征相关的特定性别肠道微生物群谱的关键驱动因素。总之，我们的研究结果表明，BTBR 小鼠 GM 的改变表现出与性别相关的显著差异，并支持使用 BTBR 小鼠模型来剖析与自闭症相关的微生物群-肠道-大脑轴改变。
