Moloney Gerard M, O'Leary Olivia F, Salvo-Romero Eloisa, Desbonnet Lieve, Shanahan Fergus, Dinan Timothy G, Clarke Gerard, Cryan John F
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
Laboratory of Neuro-Immuno-Gastroenterology, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitario Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Behav Brain Res. 2017 Sep 15;334:50-54. doi: 10.1016/j.bbr.2017.07.026. Epub 2017 Jul 20.
Increasing evidence points to a functional role of the enteric microbiota in brain development, function and behaviour including the regulation of transcriptional activity in the hippocampus. Changes in CNS miRNA expression may reflect the colonisation status of the gut. Given the pivotal impact of miRNAs on gene expression, our study was based on the hypothesis that gene expression would also be altered in the germ-free state in the hippocampus. We measured miRNAs in the hippocampus of Germ free (GF), conventional (C) and Germ free colonised (exGF) Swiss Webster mice. miRNAs were selected for follow up based on significant differences in expression between groups according to sex and colonisation status. The expression of miR-294-5p was increased in male germ free animals and was normalised following colonisation. Targets of the differentially expressed miRNAs were over-represented in the kynurenine pathway. We show that the microbiota modulates the expression of miRNAs associated with kynurenine pathway metabolism and, demonstrate that the gut microbiota regulates the expression of kynurenine pathway genes in the hippocampus. We also show a sex-specific role for the microbiota in the regulation of miR-294-5p expression in the hippocampus. The gut microbiota plays an important role in modulating small RNAs that influence hippocampal gene expression, a process critical to hippocampal development.
越来越多的证据表明肠道微生物群在大脑发育、功能和行为中发挥作用，包括对海马体转录活性的调节。中枢神经系统微小RNA（miRNA）表达的变化可能反映肠道的定植状态。鉴于miRNA对基因表达的关键影响，我们的研究基于这样的假设：在无菌状态下，海马体中的基因表达也会发生改变。我们测量了无菌（GF）、常规（C）和无菌定植（exGF）的瑞士韦伯斯特小鼠海马体中的miRNA。根据性别和定植状态，基于组间表达的显著差异选择miRNA进行后续研究。雄性无菌动物中miR-294-5p的表达增加，定植后恢复正常。差异表达miRNA的靶标在犬尿氨酸途径中过度富集。我们表明微生物群调节与犬尿氨酸途径代谢相关的miRNA的表达，并证明肠道微生物群调节海马体中犬尿氨酸途径基因的表达。我们还展示了微生物群在调节海马体中miR-294-5p表达方面的性别特异性作用。肠道微生物群在调节影响海马体基因表达的小RNA方面发挥重要作用，这一过程对海马体发育至关重要。
