APC Microbiome Ireland, University College Cork, Cork, Ireland.
711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, USA.
Neurogastroenterol Motil. 2020 Nov;32(11):e13881. doi: 10.1111/nmo.13881. Epub 2020 May 11.
Understanding the mechanisms underpinning the response to acute stress is critical for determining how this can be modulated in both health and disease and across sexes. Stress can markedly alter the microbiome and gut-brain axis signaling with the serotonergic system being particularly sensitive to acute stress. As the impact of acute stress on regional serotonergic dynamics in the gut-brain axis and the contribution of the microbiome to this are poorly appreciated, we used microbiota-deficient mice to assess whether the serotonergic response to acute stress exposure is microbiome dependent.
Adult male and female conventional, germ-free, and colonized germ-free mice underwent a single acute stressor and samples were harvested immediately or 45 minutes following stress. Serotonin and related metabolites and serotonergic gene expression were determined.
Our data clearly show the microbiota influenced gastrointestinal serotonergic response to acute stress in a sex- and region-dependent manner. Male-specific poststress increases in colonic serotonin were absent in germ-free mice but normalized following colonization. mRNA serotonergic gene expression was differentially expressed in colon and ileum of germ-free mice on a sex-dependent basis. Within the frontal cortex, absence of the microbiome altered basal serotonin, its main metabolite 5-hydroxyindoleacetic acid, and prevented stress-induced increases in serotonin turnover.
The gut microbiome influences the set points of the brain and gastrointestinal serotonergic systems and affected their response to acute stress in a sex- and region-dependent manner.
了解急性应激反应的机制对于确定如何在健康和疾病以及不同性别中调节这种反应至关重要。应激可以显著改变微生物组和肠-脑轴信号，而 5-羟色胺能系统对急性应激特别敏感。由于急性应激对肠-脑轴中区域性 5-羟色胺动力学的影响以及微生物组对此的贡献尚未得到充分认识，我们使用缺乏微生物组的小鼠来评估急性应激暴露对 5-羟色胺能反应是否依赖于微生物组。
成年雄性和雌性常规、无菌和定植无菌小鼠接受单次急性应激刺激，应激后立即或 45 分钟采集样本。测定 5-羟色胺和相关代谢物以及 5-羟色胺能基因表达。
我们的数据清楚地表明，微生物组以性别和区域依赖的方式影响胃肠道对急性应激的 5-羟色胺反应。无菌小鼠中不存在雄性特有的结肠 5-羟色胺应激后增加，但定植后恢复正常。无菌小鼠的结肠和回肠中 5-羟色胺能基因表达存在性别依赖性差异。在前额叶皮层中，微生物组的缺失改变了基础 5-羟色胺、其主要代谢物 5-羟吲哚乙酸，并阻止了应激诱导的 5-羟色胺周转率增加。
肠道微生物组影响大脑和胃肠道 5-羟色胺能系统的设定点，并以性别和区域依赖的方式影响它们对急性应激的反应。
