Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus
Open accessAbstract
Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host's behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal "depression microbiota" transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, "depression microbiota" recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in "depression microbiota" recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and "depression microbiota" recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.
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Lacking gut microbiota causes exaggerated HPA stress responses in germ-free mice.
“Research with germ-free mice shows that lacking gut microbiota causes exaggerated HPA stress responses [143].”
From Unraveling the Connections: Eating Issues, Microbiome, and Gastrointestinal Symptoms in Autism Spectrum Disorder (2025) · cites this paper as [143]
Colonization by microbiota regulates expression of critical HPA axis genes in hippocampus and modulates hippocampal serotonin concentration, which affects HPA activation.
“Colonization by microbiota has been shown to regulate the expression of critical HPA axis genes in hippocampus and modulate hippocampal serotonin concentration, which also affects HPA activation (Luo et al., 2018; Farzi et al., 2015; Shanks et al., 1995; Clarke et al., 2013).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Luo et al., 2018
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- Authors
- Luo, Y., Zeng, B., Zeng, L., Du, X., Li, B., Huo, R., Liu, L., Wang, H., Dong, M., Pan, J., Zheng, P., Zhou, C., Wei, H., & Xie, P.
- Affiliations
- Chongqing Medical University (CN)
- Army Medical University (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Flinders University (AU)
- Corresponding author
- Wei, Hong
- Xie, Peng
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2018-09-07
- Volume
- 8
- Issue
- 1
- Pages
- 187-187
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6128920
- OpenAlex
- W2890960550
- Cited by
- 245
- References
- 59
- Citations by year
- 2026: 7 · 2025: 23 · 2024: 54 · 2023: 41 · 2022: 30 · 2021: 45 · 2020: 27 · 2019: 16 · 2018: 1
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81701361)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, hippocampus, germ-free mice, depression-like behavior, anxiety-like behavior, hypothalamic-pituitary-adrenal axis, serum cortisol, lipopolysaccharide, fecal microbiota transplantation, STAT5A, AMPD3, antidepressant-like behavior
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anxiety, Behavior, Animal, Depression, Germ-Free Life, Hippocampus, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Mice, Inbred BALB C, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Psychological, Mice
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