The Royal's Institute of Mental Health Research, affiliated with the University of Ottawa, Ottawa, Ontario, Canada; Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada.
Department of Biology, Carleton University, Ottawa, Ontario, Canada.
Brain Behav Immun. 2017 Nov;66:45-55. doi: 10.1016/j.bbi.2017.06.009. Epub 2017 Jun 17.
Appreciable evidence suggests that perturbations within the gut microbiome and the immune system may play a key role in the pathogenesis of depression stemming from earlier stressful experiences. In the present investigation we examined whether microbial changes in cecum contents were associated with social avoidance behaviors, a feature of depression, and pro-inflammatory variations among socially stressed mice. Male C57BL/6 mice experienced social defeat or a control condition once a day for 10 consecutive days. Social avoidance behaviors were examined three weeks after the last defeat or control episode and blood, brain, and cecum contents were collected 24h afterward for the determination of corticosterone, pro-inflammatory cytokines, and microbial populations. Mice that were most susceptible to the behavioral effects of chronic social defeat (reflected by severe social avoidance behaviors) displayed the greatest changes within particular sets of bacteria at the phylum and genus taxonomic ranks. Although plasma and brain cytokines were not significantly altered in socially defeated mice, changes in the mRNA expression of interleukin (IL)-1β and IL-6 within the prefrontal cortex were associated with elevated abundance of Flavobacterium spp. and reduced abundance of Turicibacter spp., which were also strongly correlated to social avoidance severity. Although at this time a causal connection cannot be inferred, these results point to the possibility that specific clusters of bacterial communities in cecum contents may be linked to vulnerability to social deficits stemming from prolonged social stressor experiences.
大量证据表明,肠道微生物组和免疫系统的紊乱可能在源于早期应激经历的抑郁症发病机制中起关键作用。在本研究中,我们研究了盲肠内容物中的微生物变化是否与社会回避行为(抑郁症的一个特征)以及社交应激小鼠中的促炎变化有关。雄性 C57BL/6 小鼠每天接受一次社交挫败或对照条件,持续 10 天。最后一次挫败或对照后三周检查社会回避行为,随后 24 小时采集血液、大脑和盲肠内容物,以测定皮质酮、促炎细胞因子和微生物种群。最易受慢性社交挫败行为影响的小鼠(表现为严重的社会回避行为)在特定的细菌门和属分类等级中表现出最大的变化。尽管社交挫败小鼠的血浆和大脑细胞因子没有明显改变,但前额叶皮质中白细胞介素(IL)-1β和 IL-6 的 mRNA 表达变化与 Flavobacterium spp. 的丰度增加和 Turicibacter spp. 的丰度降低有关,这两者也与社会回避严重程度呈强烈相关。虽然目前还不能推断出因果关系,但这些结果表明,盲肠内容物中特定的细菌群落簇可能与源于长期社交应激体验的社交缺陷易感性有关。