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:
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.
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
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