An increasing number of studies have recently indicated the important effects of gut microbes on various functions of the central nervous system. However, the underlying mechanisms by which gut microbiota regulate brain functions and behavioral phenotypes remain largely unknown. We therefore used isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis to obtain proteomic profiles of the hippocampus in germ-free (GF), colonized GF, and specific pathogen-free (SPF) mice. We then integrated the resulting proteomic data with previously reported mRNA microarray data, to further explore the effects of gut microbes on host brain functions. We identified that 61 proteins were upregulated and 242 proteins were downregulated in GF mice compared with SPF mice. Of these, 124 proteins were significantly restored following gut microbiota colonization. Bioinformatic analysis of these significant proteins indicated that the glucocorticoid receptor signaling pathway and inflammation-related pathways were the most enriched disrupted pathways. This study provides new insights into the pathological mechanisms of gut microbiota-regulated diseases.

中文翻译：

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肠道菌群的调节破坏了小鼠海马中糖皮质激素受体途径和炎症相关途径。

最近越来越多的研究表明肠道微生物对中枢神经系统各种功能的重要影响。然而，肠道菌群调节大脑功能和行为表型的潜在机制仍然未知。因此，我们使用等压标记进行基于相对和绝对定量（iTRAQ）的定量蛋白质组分析，以在无菌（GF），定植的GF和特定的无病原体（SPF）小鼠中获得海马的蛋白质组学特征。然后，我们将所得的蛋白质组学数据与先前报道的mRNA芯片数据进行整合，以进一步探索肠道微生物对宿主脑功能的影响。我们发现与SPF小鼠相比，GF小鼠中61个蛋白被上调，而242个蛋白被下调。这些，肠道菌群定殖后，124种蛋白质被显着恢复。这些重要蛋白质的生物信息学分析表明，糖皮质激素受体信号传导途径和炎症相关途径是最丰富的破坏途径。这项研究提供了新的见解，肠道菌群调节疾病的病理机制。