2. Academic Validation
  3. Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function

Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function

  • NPJ Biofilms Microbiomes. 2024 Oct 28;10(1):111. doi: 10.1038/s41522-024-00582-w.
Guanhao Wang # 1 2 3,  Lining Cao # 1,  Shuanqing Li 1,  Meihui Zhang 1,  Yingqi Li 1 2 3,  Jinjin Duan 1,  You Li 1,  Zhangsen Hu 1,  Jiaan Wu 1,  Jianbo Ni 4,  Danmei Lan 1,  Tianming Li 1,  Jianfeng Lu 5 6
Affiliations

Affiliations

  • 1 Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 2 Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 3 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • 4 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 5 Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. Lu.jianfeng@tongji.edu.cn.
  • 6 Suzhou Institute of Tongji University, Suzhou, China. Lu.jianfeng@tongji.edu.cn.
  • # Contributed equally.
PMID: 39468065 DOI: 10.1038/s41522-024-00582-w
Abstract

The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients. Fecal metabolic profiling exposed remarkable increase of gut ceramides in CORT-treated and recipient mice. Oral gavage with Bifidobacterium pseudolongum and Lactobacillus reuteri could induce elevations of gut ceramides in mice. Ceramides-treated mice showed depressive-like phenotypes, significant downregulation of oxidative phosphorylation-associated genes, and hippocampal mitochondrial dysfunction. Our study demonstrated a link between chronic exposure to CORT and its impact on GM composition, which induces ceramides accumulation, ultimately leading to hippocampal mitochondrial dysfunction. This cascade of events plays a critical role in reducing adult hippocampal neurogenesis and is strongly associated with the development of depression-like behaviors.

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