Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis

Frontiers in Cellular and Infection Microbiology

Cheng, Ke¹  Luo, Yuanyuan²  Wang, Haiyang³  Wei, Hong³  Huo, Ran³  Fang, Liang³  Zeng, Benhua⁴  Xie, Peng⁴  Li, Bo⁴  Li, Wenxia⁴  Zhou, Chanjuan⁴  Zeng, Li⁵  Niu, Rong⁵ 

[1] Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, China;Department of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, China;Department of Neurology, Yongchuan Hospital, Chongqing Medical University, China;Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, China;Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Department of Laboratory Medicine, Chongqing Medical University, China

关键词: Intestinal microbes;    HPA axis;    CRS model;    Microbiota-gut-brain axis;    stress-related diseases.;   

DOI  :  10.3389/fcimb.2017.00489

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

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 hours 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.

【 授权许可】

CC BY