AUTHOR=Qi Xunzhong , Zhong Xiaogang , Xu Shaohua , Zeng Benhua , Chen Jianjun , Zang Guangchao , Zeng Li , Bai Shunjie , Zhou Chanjuan , Wei Hong , Xie Peng 

TITLE=Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota

JOURNAL=Frontiers in Genetics

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00520

DOI=10.3389/fgene.2020.00520

ISSN=1664-8021

ABSTRACT=BACKGROUND:
In previous studies, our team examined 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 selected for validation experiment.

RESULTS: 
Compared with GF mice, 243 DEGs were identified in CGF mice. The most enriched KEGG pathways associated with upregulated genes were “protein digestion and absorption”, “extracellular matrix (ECM)-receptor interaction”, and “focal adhesion”. Compared with HC mice, 642 differentially expressed genes were identified in MDD 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 highly correlated in PPI network analysis.

CONCLUSIONS: 
In summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota, and inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.