BACKGROUND Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. METHODS To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. RESULTS Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. CONCLUSIONS Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. Video abstract.

中文翻译：

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发酵饮料开菲尔对小鼠宿主行为，免疫力和微生物组肠脑模块的不同作用。

背景技术越来越多的证据表明，肠道微生物群通过沿肠道-脑轴的双向通信在调节脑生理和行为中发挥作用。因此，肠道菌群代表了潜在的治疗靶标，可影响中央介导的事件和宿主行为。因此，值得注意的是，最近已显示出发酵乳饮料开菲尔可调节小鼠肠道菌群的组成。目前尚不清楚kefirs是否对微生物菌群-肠脑轴有不同的影响，以及它们本身是否可以调节宿主行为。方法为了解决这个问题，对经过一系列测试以表征其行为表型的小鼠施用了两种不同的酮（Fr1和UK4）或未发酵的牛奶对照。此外，回弹的met弹枪宏基因组测序 进行粪便和粪便处理，以及粪便代谢组学分析。最后，评估了全身免疫措施和肠道血清素水平。统计学分析是通过ANOVA进行的，随后是Dunnett的事后检验或Kruskal-Wallis检验，然后是Mann-Whitney U检验。结果Fr1改善了应激引起的结肠血清素能信号传导的减少以及糖精偏好测试中的奖励寻求行为。另一方面，UK4减少了重复行为并减轻了压力诱导的奖励行为中的缺陷。此外，UK4增加了恐惧相关的上下文记忆，但减少了灌胃对长期空间学习的改善。在外周免疫系统中，UK4增加了Treg细胞和白介素10的水平，而Fr1改善了牛奶管饲法引起的中性粒细胞水平和CXCL1水平升高。对肠道菌群的分析表明，两种酮均显着改变了宿主菌群的组成和功能能力，其中特定细菌种类以开菲尔依赖性方式改变。此外，两个kefirs都增加了肠道菌群产生GABA的能力，这与罗伊氏乳杆菌的患病率增加有关。结论总而言之，这些数据表明开菲尔可以通过微生物-肠道-免疫-脑轴发出信号，并调节宿主行为。另外，不同的kefirs可能将微生物群引向不同的免疫和行为调节作用。这些结果表明开菲尔可以积极调节微生物群-肠-脑轴的特定方面，并支持扩大精神药物的定义，使其包括开菲尔发酵食品。录像摘要。