Qi Xunzhong, Zhong Xiaogang, Xu Shaohua, Zeng Benhua, Chen Jianjun, Zang Guangchao, Zeng Li, Bai Shunjie, Zhou Chanjuan, Wei Hong, Xie Peng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
Front Genet. 2020 Jun 25;11:520. doi: 10.3389/fgene.2020.00520. eCollection 2020.
In previous studies, our team examined the gut microbiota of healthy individuals and depressed patients using fecal microbiota transplantation of germ-free (GF) mice. Our results showed that depression-like and anxiety-like behavioral phenotypes of host mice were increased, but the molecular mechanism by which gut microbiota regulate host behavioral phenotypes is still unclear.
To investigate the molecular mechanism by which gut microbiota regulate host brain function, adult GF mice were colonized with fecal samples derived from healthy control (HC) individuals or patients with major depressive disorder (MDD). Transcriptomic profiling of hypothalamus samples was performed to detect differentially expressed genes (DEGs). qRT-PCR was used for validation experiments.
Colonization germ-free (CGF) mice had 243 DEGs compared with GF mice. The most enriched KEGG pathways associated with upregulated genes were "protein digestion and absorption," "extracellular matrix (ECM)-receptor interaction," and "focal adhesion." MDD mice had 642 DEGs compared with HC mice. The most enriched KEGG pathways associated with upregulated genes in MDD mice were also "protein digestion and absorption," "ECM-receptor interaction," and "focal adhesion." Meanwhile, the most enriched KEGG pathway associated with downregulated genes in these mice was "oxidative phosphorylation," and genes related to this pathway were found to be highly correlated in PPI network analysis.
In summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota and that inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.
在先前的研究中，我们团队通过无菌（GF）小鼠的粪便微生物群移植，研究了健康个体和抑郁症患者的肠道微生物群。我们的结果显示，宿主小鼠的抑郁样和焦虑样行为表型有所增加，但肠道微生物群调节宿主行为表型的分子机制仍不清楚。
为了研究肠道微生物群调节宿主脑功能的分子机制，将来自健康对照（HC）个体或重度抑郁症（MDD）患者的粪便样本定殖于成年GF小鼠。对下丘脑样本进行转录组分析，以检测差异表达基因（DEG）。采用qRT-PCR进行验证实验。
与GF小鼠相比，定殖无菌（CGF）小鼠有243个DEG。与上调基因相关的最丰富的KEGG通路是“蛋白质消化和吸收”、“细胞外基质（ECM）-受体相互作用”和“粘着斑”。与HC小鼠相比，MDD小鼠有642个DEG。MDD小鼠中与上调基因相关的最丰富的KEGG通路也是“蛋白质消化和吸收”、“ECM-受体相互作用”和“粘着斑”。同时，这些小鼠中与下调基因相关的最丰富的KEGG通路是“氧化磷酸化”，并且在蛋白质-蛋白质相互作用（PPI）网络分析中发现与该通路相关的基因高度相关。
总之，我们的研究结果表明，ECM的调节是不同肠道微生物群共有的关键机制，并且来自MDD患者的肠道微生物群对下丘脑能量代谢的抑制是行为调节和抑郁症的潜在机制。
