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

Authors Liu S, Guo R, Liu F, Yuan Q, Yu Y, Ren F

Received 27 December 2019

Accepted for publication 1 March 2020

Published 31 March 2020 Volume 2020:16 Pages 859—869


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Jun Chen

Shuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1

1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China; 3College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 4Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of China

Correspondence: Rongjuan Guo
Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan 1st Block, Fengtai District, Beijing City, People’s Republic of China
Tel +86 1 861 137 7633
Fax +86 1064286498

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.

Keywords: gut microbiota, depression, neurotransmitter, HPA axis, immune, mitochondrial

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