Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota
Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota
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细胞外基质和氧化磷酸化：肠道微生物群调节下丘脑功能的重要作用
DOI：
10.3389/fgene.2020.00520
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
Peng Xie
中科院分区：
文献类型：
--
作者：
Xunzhong Qi;Xiaogang Zhong;Shaohua Xu;Benhua Zeng;Jianjun Chen;Guangchao Zang;Li Zeng;Shunjie Bai;Hong Wei;Peng Xie
在以前的研究中，我们的团队使用无菌（GF）小鼠的粪便微生物群移植检查了健康个体和抑郁症患者的肠道微生物群。我们的研究结果表明，宿主小鼠的抑郁样和焦虑样行为表型增加，但肠道微生物群调节宿主行为表型的分子机制仍不清楚。方法采用健康对照组（HC）和抑郁症（MDD）患者的粪便样本对成年GF小鼠进行定植，研究肠道菌群调节宿主脑功能的分子机制。对下丘脑样品进行转录组学分析以检测差异表达基因（DEG）。qRT-PCR用于验证实验。结果定植无菌（CGF）小鼠与GF小鼠相比，DEG为243个。与上调基因相关的最丰富的KEGG途径是“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小鼠具有642个DEG。与MDD小鼠中上调基因相关的最丰富的KEGG途径也是“蛋白质消化和吸收”、“ECM-受体相互作用”和“粘着斑”。同时，在这些小鼠中，与下调基因相关的最丰富的KEGG途径是“氧化磷酸化”，并且在PPI网络分析中发现与该途径相关的基因高度相关。结论总之，我们的研究结果表明，ECM的调节是不同肠道菌群共享的关键机制，来自MDD患者的肠道菌群抑制下丘脑的能量代谢是行为调节和抑郁症的潜在机制。
Background 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. Methods 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. Results 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. Conclusion 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.
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DOI：
10.1073/pnas.062183499
发表时间：
2002-05-14
影响因子：
11.1
作者：
Than, ME;Henrich, S;Bode, W
通讯作者：
Bode, W
DOI：
10.1111/ejn.13291
发表时间：
2016-11
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Luczynski P;Whelan SO;O'Sullivan C;Clarke G;Shanahan F;Dinan TG;Cryan JF
通讯作者：
Cryan JF
DOI：
10.1084/jem.20100222
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Falet H;Pollitt AY;Begonja AJ;Weber SE;Duerschmied D;Wagner DD;Watson SP;Hartwig JH
通讯作者：
Hartwig JH
微生物群调节下丘脑-垂体-肾上腺轴的焦虑样行为和内分泌异常。
影响因子：
5.7
作者：
Huo R;Zeng B;Zeng L;Cheng K;Li B;Luo Y;Wang H;Zhou C;Fang L;Li W;Niu R;Wei H;Xie P
通讯作者：
Xie P
影响因子：
3.8
作者：
Beauchemin, AMJ;Gottlieb, B;Trifiro, MA
通讯作者：
Trifiro, MA