Lyte J M, Proctor A, Phillips G J, Lyte M, Wannemuehler M
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, 50011 USA; Alimentary Pharmabiotic Centre Microbiome Institute, University College Cork, Cork, Ireland.
Department of Veterinary Microbiology & Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA.
Behav Brain Res. 2019 Jan 1;356:221-226. doi: 10.1016/j.bbr.2018.08.022. Epub 2018 Aug 25.
Despite considerable attention, the mechanisms by which the microbiota affect brain function and host behaviour via the gut-brain axis remain undefined. Identifying microbe-specific pathways that influence neuronal function and bi-directional communication between the gut microbiota and the host central nervous system is challenging due to the extreme microbial diversity in the gut of conventionally-reared mice. Herein, we describe the use of the altered Schaedler flora (ASF) mouse model as an alternative to conventionally-reared and germ-free animals. Colonized with only 8 bacterial species, use of ASF mice greatly simplifies the examination of microbiota-host interactions. We assessed the extent to which behaviour differed between mice with a limited consortium of bacteria compared with a complex, conventional microbiota. The elevated plus maze and open-field assays were utilized to assess murine behaviour. Histological analysis of ileum and colon was performed to evaluate intestinal morphology, and 16 s rRNA gene taxonomic profiling was performed to determine host-stress induced changes in fecal microbial communities. Behavioural and serum corticosterone differences were observed between ASF and conventionally-reared mice, while no differences were found between the intestinal morphology of these two groups. The stress of the behavioural tests induced significant changes in the ASF fecal microbial community but not in that of the conventionally-reared mice. In contrast to the conventionally-reared mice, the results indicated that the ASF mice displayed a marked anxiogenic-like behaviour. These data indicate that ASF mice represent a unique model to elucidate mechanisms governing microbiota-gut-brain communication affecting behaviour.
尽管受到了广泛关注，但微生物群通过肠-脑轴影响大脑功能和宿主行为的机制仍不明确。由于传统饲养小鼠肠道中微生物的极端多样性，确定影响神经元功能以及肠道微生物群与宿主中枢神经系统之间双向通信的微生物特异性途径具有挑战性。在此，我们描述了使用改变的舍德勒菌群（ASF）小鼠模型作为传统饲养动物和无菌动物的替代方案。ASF小鼠仅定殖有8种细菌，其使用极大地简化了微生物群与宿主相互作用的研究。我们评估了与复杂的传统微生物群相比，具有有限细菌群落的小鼠之间行为的差异程度。利用高架十字迷宫和旷场试验来评估小鼠行为。对回肠和结肠进行组织学分析以评估肠道形态，并进行16S rRNA基因分类分析以确定宿主应激诱导的粪便微生物群落变化。在ASF小鼠和传统饲养小鼠之间观察到行为和血清皮质酮的差异，而这两组的肠道形态没有差异。行为测试的应激在ASF粪便微生物群落中诱导了显著变化，但在传统饲养小鼠的粪便微生物群落中未诱导出变化。与传统饲养小鼠相反，结果表明ASF小鼠表现出明显的焦虑样行为。这些数据表明，ASF小鼠是一种独特的模型，可用于阐明控制微生物群-肠道-脑通信影响行为的机制。
