Microbiota modulate anxiety-like behavior and endocrine abnormalities in hypothalamic-pituitary-adrenal axis
Open accessAbstract
Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA) axis under stress. We tested germ-free (GF) mice and specific pathogen-free (SPF) mice, divided into four groups. A chronic restraint stress (CRS) protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.
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Following chronic restraint stress, germ-free mice showed significantly greater HPA axis activity, whereas SPF mice exhibited more anxiety-like behaviors under the same stress.
“Following chronic restraint stress, germ-free mice showed significantly greater HPA axis activity, whereas the SPF mice exhibited more anxiety-like behaviors under the same stress (349).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [349]
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The Brain–Gut–Bone Axis in Neurodegenerative Diseases: Insights, Challenges, and Future Prospects
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- Authors
- Huo, R., Zeng, B., Zeng, L., Cheng, K., Li, B., Luo, Y., Wang, H., Zhou, C., Fang, L., Li, W., Niu, R., Wei, H., & Xie, P.
- Affiliations
- Chongqing Medical University (CN)
- Army Medical University (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- Wei, Hong
- Xie, Peng
- Venue
- Frontiers in Cellular and Infection Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2017-11-30
- Volume
- 7
- Pages
- 489-489
- ISSN
- 2235-2988 (ISSN-L)
- PMC
- PMC5715198
- OpenAlex
- W2770969221
- Cited by
- 221
- References
- 62
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 34 · 2023: 18 · 2022: 34 · 2021: 47 · 2020: 26 · 2019: 16 · 2018: 8
- FWCI
- 7.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81401140, 81601207)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, anxiety-like behavior, hypothalamic-pituitary-adrenal axis, germ-free mice, chronic restraint stress, corticotropin-releasing factor, ACTH, corticosterone, aldosterone, CRH receptor 1, mineralocorticoid receptor, stress response, neuroendocrine system, stress-related disorders
- MeSH terms
- Gastrointestinal Microbiome, CRF Receptor, Type 1, Adrenocorticotropic Hormone, Aldosterone, Animals, Anxiety, Behavior, Animal, Corticotropin-Releasing Hormone, Germ-Free Life, Hormones, Hypothalamo-Hypophyseal System, Intestines, Male, Pituitary-Adrenal System, RNA, Messenger, Stress, Psychological, Receptors, Corticotropin-Releasing Hormone, Receptors, Mineralocorticoid, Mice
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