Gut microbiota can affect multiple brain functions and cause behavioral alterations through the microbiota-gut-brain axis. In our previous study, we found that the absence of gut microbiota can influence the expression of microRNAs and mRNAs in the hippocampal region of the germ-free (GF) mice. Long non-coding RNAs (lncRNAs) are increasingly being recognized as an important functional transcriptional regulator in the brain. In the present study, we aim to identify possible biological pathways and functional networks for lncRNA-associated transcript of the gut microbiota in relation to the brain function. The profiles of lncRNA and mRNA from specific pathogen-free (SPF), colonized GF (CGF), and GF mice were generated using the Agilent Mouse LncRNA Array v2.0. Differentially expressed (DE) lncRNAs and mRNAs were identified, and lncRNA target genes were also predicted. Ingenuity pathway analysis (IPA) was performed to analyze related signaling pathways and biological functions associated with these dysregulated mRNAs and target genes. Validation with quantitative real-time PCR was performed on several key genes. Compared with SPF mice a total of 2230 DE lncRNAs were found in GF mice. Among these, 1355 were upregulated and 875 were downregulated. After comparing the target genes of DE lncRNAs with mRNA datasets, 669 overlapping genes were identified. IPA core analyses revealed that most of these genes were highly associated with cardiac hypertrophy, nuclear factors of activated T cells (NFAT) gonadotropin-releasing hormone (GnRH), calcium, and cAMP-response element-binding protein (CREB) signaling pathways. Additionally, mRNA expression levels of APP, CASP9, IGFBP2, PTGDS, and TGFBR2 genes that are involved in central nervous system functions were significantly changed in the GF mouse hippocampus. Through this study, for the first time, we describe the effect of gut microbiota on the hippocampal lncRNA regulation. This will help in enhancing the overall knowledge about microbiota-gut-brain axis.

中文翻译：

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海马特异性调节无菌小鼠中较长的非编码RNA和mRNA表达。

肠道菌群可以影响多种大脑功能，并通过菌群-肠脑轴引起行为改变。在我们之前的研究中，我们发现肠道菌群的缺失会影响无菌（GF）小鼠海马区microRNA和mRNA的表达。长非编码RNA（lncRNA）越来越被认为是大脑中重要的功能性转录调节因子。在本研究中，我们旨在确定与肠道功能有关的肠道菌群与lncRNA相关的转录本的可能的生物学途径和功能网络。使用安捷伦Mouse LncRNA Array v2.0生成了无特定病原体（SPF），定植的GF（CGF）和GF小鼠的lncRNA和mRNA谱。鉴定了差异表达（DE）lncRNA和mRNA，还预测了lncRNA靶基因。进行了独创性途径分析（IPA），以分析与这些失调的mRNA和靶基因相关的相关信号传导途径和生物学功能。对几个关键基因进行了定量实时PCR的验证。与SPF小鼠相比，在GF小鼠中共发现2230个DE lncRNA。其中，上调了1355个，下调了875个。将DE lncRNA的靶基因与mRNA数据集进行比较后，鉴定出669个重叠基因。IPA核心分析显示，这些基因大多数与心肌肥大，活化T细胞（NFAT）促性腺激素释放激素（GnRH）的核因子，钙和cAMP反应元件结合蛋白（CREB）信号通路高度相关。此外，APP，CASP9，IGFBP2，在GF小鼠海马中，涉及中枢神经系统功能的PTGDS和TGFBR2基因发生了显着变化。通过这项研究，我们首次描述了肠道菌群对海马lncRNA调控的作用。这将有助于增强有关微生物群-肠脑轴的整体知识。