a Piglet Nutrition & Cognition Laboratory , University of Illinois , Urbana , IL , USA.
b Neuroscience Program , University of Illinois , Urbana , IL , USA.
Gut Microbes. 2017 Nov 2;8(6):589-600. doi: 10.1080/19490976.2017.1353849. Epub 2017 Aug 18.
A dynamic relationship between the gut microbiota and brain is pivotal in neonatal development. Dysbiosis of the microbiome may result in altered neurodevelopment; however, it is unclear which specific members of microbiota are most influential and what factors might mediate the relationship between the gut and the brain. Twenty-four vaginally-derived male piglets were subjected to magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces, and blood were collected and analyzed for volatile fatty acids, microbiota relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation analysis was performed to assess the mediatory effect of serum biomarkers on the relationship between microbiota and neurometabolites. Results indicated fecal Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis of serum biomarkers indicated Ruminococcus independently predicted serum serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a significant indirect effect (i.e., the effect of fecal Ruminococcus through cortisol on NAA) was observed and the direct effect became insignificant. Thus, serum cortisol fully mediated the relationship between fecal Ruminococcus and brain NAA. Using magnetic resonance spectroscopy, this study used a statistical mediation analysis and provides a novel perspective into the potential underlying mechanisms through which the microbiota may shape brain development. This is the first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings are substantiated by previous literature indicating these factors may be influential in the etiology of neurodevelopmental disorders.
肠道微生物群与大脑之间的动态关系对新生儿的发育至关重要。微生物群的失调可能导致神经发育改变；然而，目前尚不清楚哪种特定的微生物群成员最具影响力，以及哪些因素可能调节肠道和大脑之间的关系。24 只阴道分娩的雄性仔猪在 30 日龄时接受磁共振波谱分析。分别采集升结肠内容物、粪便和血液，用于分析挥发性脂肪酸、16s rRNA 相对丰度的微生物群和血清代谢物。进行中介分析以评估血清生物标志物对微生物群和神经代谢物之间关系的中介效应。结果表明，粪便中的 Ruminococcus 和 Butyricimonas 预测大脑中的 N- 乙酰天冬氨酸 (NAA)。血清生物标志物分析表明，Ruminococcus 独立预测血清中的血清素和皮质醇。三步中介分析表明：i）Ruminococcus 负向预测 NAA，ii）Ruminococcus 负向预测皮质醇，iii）观察到显著的间接效应（即粪便 Ruminococcus 通过皮质醇对 NAA 的影响），直接效应变得无统计学意义。因此，血清皮质醇完全介导了粪便 Ruminococcus 与大脑 NAA 之间的关系。本研究使用磁共振波谱，通过统计中介分析，提供了一个新的视角，了解微生物群可能影响大脑发育的潜在机制。这是首次将 Ruminococcus、皮质醇和 NAA 在体内联系起来的研究，并且这些发现得到了先前文献的支持，表明这些因素可能在神经发育障碍的发病机制中具有影响力。
