Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway.


Author: Liu S1, Guo R2, Liu F3, Yuan Q4, Yu Y1, Ren F1

Affiliation: <sup>1</sup>Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.

<sup>2</sup>Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People's Republic of China.

<sup>3</sup>College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People's Republic of China.

<sup>4</sup>Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People's Republic of China.
Conference/Journal: Neuropsychiatr Dis Treat.
Date published: 2020 Mar 31
Other:
 Volume ID: 16   ,  Pages: 859-869   ,  Special Notes: doi: 10.2147/NDT.S243551. eCollection  2020.   ,  Word Count: 274  
    Purpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.



Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.



Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.



Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.



© 2020 Liu et al.



KEYWORDS: HPA axis; depression; gut microbiota; immune; mitochondrial; neurotransmitter



PMID: 32280227 PMCID: PMC7127849 DOI: 10.2147/NDT.S243551