Exp Neurobiol.  2021 Feb;30(1):59-72. 10.5607/en20055.

Regulation of Gut Microbiota Disrupts the Glucocorticoid Receptor Pathway and Inflammation-related Pathways in the Mouse Hippocampus

Affiliations
  • 1College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China
  • 2NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China,
  • 3Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China
  • 4College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China
  • 5Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China
  • 6Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

Abstract

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.

Keyword

Germ-free; Gut microbiota; Proteomics; Hippocampus; Glucocorticoid receptor pathway; Inflammation-related pathways
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