Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model
Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model
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小鼠模型中微生物群-肠-脑轴内微生物反应中压力与性别之间的相互作用
DOI：
10.1097/psy.0000000000000572
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发表时间：
2018
影响因子：
3.3
通讯作者：
M. Lyte
中科院分区：
文献类型：
--
作者：
Matthew C. B. Tsilimigras;R. Gharaibeh;Michael Sioda;L. Gray;A. Fodor;M. Lyte
目的动物模型经常用于研究应激反应，但实验很少包括雌性。微生物-肠道-脑轴与行为应激反应之间的联系在这里使用混合性别小鼠队列进行了研究。方法对CF-1小鼠进行为期19天（雄性8只，雌性8只）的交替约束和强迫游泳，与数量匹配的对照动物进行对照，并对其肠道微生物群的16S rRNA基因进行测序。考虑压力状态和性别的混合线性模型，将个体嵌套在笼子中以控制笼子效应，对这些数据进行了评估。研究小鼠在高架加迷宫、开阔地和明暗箱中的行为。结果性别、压力及其相互作用与社区水平的相关性显著。男性的微生物多样性高于女性（p = 0.025）。在至少25%的样本中检测到的638个操作分类单元中，有94个操作分类单元是显著的：31个（应激），61个（性别）和34个（性别-应激相互作用）。39项行为测量中有20项对压力有显著性意义，3项对性压力有显著性意义，6项对性压力有显著性意义。然而，没有发现行为措施与特定微生物之间的显著关联。这些数据表明，性别影响应激反应和微生物-肠-脑轴，因此，考虑性别差异如何驱动行为和微生物群落结构，对行为和微生物组的研究将受益。宿主的应激恢复能力和应激诱导行为与特定微生物之间缺乏关联表明，下丘脑-垂体-肾上腺轴的激活代表了微生物对宿主行为影响的一个阈值。未来的研究需要检验性别、应激反应和微生物-肠道-脑轴的交叉关系。
Objective Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. Methods CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Results Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. Conclusions These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.