Data_Sheet_1_Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota.PDF

BackgroundIn 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.MethodsTo 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.ResultsColonization 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.ConclusionIn 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，本团队通过对无菌（GF）小鼠进行粪便微生物群移植，探究了健康个体及抑郁症患者的肠道微生物群。研究结果表明，宿主小鼠的抑郁样及焦虑样行为表型有所增加，然而，调节宿主行为表型的肠道微生物群的分子机制尚不明确。研究方法方面，为探究肠道微生物群调节宿主脑功能的作用机制，成年无菌小鼠被移植了来自健康对照组（HC）个体或重度抑郁症（MDD）患者的粪便样本。通过对下丘脑样本进行转录组分析，以检测差异表达基因（DEGs）。定量逆转录聚合酶链反应（qRT-PCR）被用于验证实验。研究结果方面，与无菌小鼠相比，移植菌群无菌（CGF）小鼠具有243个DEGs。与上调基因最相关的富集KEGG通路包括“蛋白质消化和吸收”、“细胞外基质（ECM）-受体相互作用”以及“焦点粘附”。与HC小鼠相比，MDD小鼠具有642个DEGs。与MDD小鼠上调基因最相关的富集KEGG通路同样为“蛋白质消化和吸收”、“ECM-受体相互作用”以及“焦点粘附”。同时，与这些小鼠下调基因最相关的KEGG通路为“氧化磷酸化”，而在蛋白质互作网络（PPI）分析中发现，与该通路相关的基因表现出高度相关性。结论方面，综上所述，我们的研究结果表明，细胞外基质的调节是不同肠道微生物群共有的关键机制，而MDD患者来源的肠道微生物群抑制下丘脑的能量代谢可能是行为调节和抑郁症的潜在机制。