Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, C238, 12850 East Montview Blvd, Aurora, CO 80045, USA.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, C238, 12850 East Montview Blvd, Aurora, CO 80045, USA.
Neuroscience. 2019 Feb 1;398:206-217. doi: 10.1016/j.neuroscience.2018.11.048. Epub 2018 Dec 15.
The central nervous system (CNS) and gastrointestinal tract (GIT) are linked through neuro-endocrine and humoral pathways. Critically ill patients suffer severe physical and emotional stress and frequently receive acid suppressants; however, stress and acid suppression may alter GIT microbiota. This study evaluated the effects of acid suppression on the GIT microbiota and genome-wide expression of brain-specific genes in a murine model of restraint stress. Twenty-four male C57BL/6J mice were randomly assigned to three days of restraint stress by hypothermic immobilization or control environment for three hours daily and either esomeprazole 2 mg/kg or saline by intraperitoneal injection daily. Bacterial communities associated with the stomach, ileum, cecum, and mid-colon were determined by broad-range 16S rRNA gene sequencing, while RNA-sequencing assessed mRNA expression in the hippocampus. Both stress (p < 0.001) and esomeprazole (p = 0.006) had significant, independent effects on the composition of stomach microbiota. Stress had no impact on the hippocampus but the addition of esomeprazole induced differential expression of 124 genes, many of which are involved in cognitive and behavior pathways. Gene expression was correlated with the abundances of multiple microbial families. Acute stress has region-specific effects on the distribution of GIT commensal bacteria which is heightened with acid suppression. Several key biological processes in the hippocampus that are needed for neurocognition are affected by dysbiosis caused by acid suppression during stress. Further studies should evaluate associations between microbiota, host gene expression, the abundance of CNS neurocognitive modulators, and their impact on cognition and behavior.
中枢神经系统（CNS）和胃肠道（GIT）通过神经内分泌和体液途径相连。危重症患者遭受严重的身体和情绪压力，经常接受酸抑制剂治疗；然而，压力和酸抑制可能会改变 GIT 微生物群。本研究评估了酸抑制对束缚应激小鼠模型中 GIT 微生物群和大脑特异性基因全基因组表达的影响。24 只雄性 C57BL/6J 小鼠随机分为三组，每天进行 3 天的低温固定束缚应激或对照环境 3 小时，并每天通过腹腔注射给予埃索美拉唑 2mg/kg 或生理盐水。通过广谱 16S rRNA 基因测序确定与胃、回肠、盲肠和结肠中段相关的细菌群落，同时通过 RNA 测序评估海马中的 mRNA 表达。应激（p<0.001）和埃索美拉唑（p=0.006）都对胃微生物群的组成有显著的独立影响。应激对海马没有影响，但埃索美拉唑的添加诱导了 124 个基因的差异表达，其中许多基因参与认知和行为途径。基因表达与多个微生物家族的丰度相关。急性应激对 GIT 共生细菌的分布有特定区域的影响，而酸抑制则加剧了这种影响。在应激期间酸抑制引起的微生物失调会影响海马体中几个对神经认知至关重要的关键生物学过程。应进一步研究评估微生物群、宿主基因表达、中枢神经系统神经认知调节剂的丰度及其对认知和行为的影响之间的关联。
