The Gut Microbiome Modulates the Changes in Liver Metabolism and in Inflammatory Processes in the Brain of Chronic Unpredictable Mild Stress Rats
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Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.
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FMT from CUMS mice to germ-free mice resulted in increased anxiety and depression-like behaviour in three studies.
“When investigating the effects of FMT from CUMS mice to germ free mice, three studies found that the FMT resulted in increased anxiety and depression-like behaviour [21–23].”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [22]
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- Authors
- Lv, W.-J., Wu, X.-L., Chen, W.-Q., Li, Y.-F., Zhang, G.-F., Chao, L.-M., Zhou, J.-H., Guo, A., Liu, C., & Guo, S.-N.
- Affiliations
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China
- Zhaoqing Medical College (CN)
- Zhaoqing Medical College, Zhaoqing, Guangdong 526020, China
- South China Agricultural University (CN)
- Corresponding author
- Liu, Cui
- ORCID
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2019-10-24
- Volume
- 2019
- Pages
- 1-14
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC6854967
- OpenAlex
- W2982172561
- Cited by
- 61
- References
- 56
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 3 · 2023: 9 · 2022: 14 · 2021: 11 · 2020: 7
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Department of Agriculture of Guangdong Province (31472232)
- National Natural Science Foundation of China (31472232)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, depression, chronic unpredictable mild stress, microbiota-gut-brain axis, fecal microbiota transplantation, gut dysbiosis, intestinal barrier integrity, zonulin, fatty acid binding protein 2, metabolic liver disease, astrocyte activation, neuroinflammation, inflammatory cytokines
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Chronic Disease, Depression, Disease Models, Animal, Humans, Inflammation, Liver, Male, Stress, Psychological, Rats, Metabolomics
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