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

Abstract

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.

Loss of T cells influences sex differences in stress-related gene expression

“…Data shown are mean +/− SEM. Statistically significant differences between genotypes are denoted by *p < .05. levels in response to repeated restraint stress (Huo et al, 2017). CRHR2 has been shown to play an inverse role by regulating and dampening the stress response mounted by CRH; mice lacking CRHR2 show a hypersensitive HPA axis responses to stress and persistently elevated corticosterone levels after stress (Coste et al, 2000;Bale et al, 2000).…”

Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders

“…FMT is commonly used in the treatment of GI diseases such as Clostridium difficile infection, Crohn's disease, and ulcerative colitis (Anderson, Edney, & Whelan, 2012; Aroniadis & Brandt, 2013; Xu et al, 2015). A study reported that FMT from depressed individuals causes depression‐like behaviors in mice (Gareau et al, 2011; Huo et al, 2017). Moreover, obese‐type intestinal microbiota induce neurobehavioral changes in the absence of obesity which is linked to the prevalence of mental illness, particularly depression and dementia (Bruce‐Keller et al, 2015).…”

Bottoms up: the role of gut microbiota in brain health

“…Mouse models of anxiety, depression and stress also frequently have altered microbiota composition, and germ-free mice lacking a microbiota display reduced stress and depressive behaviour (Park et al, 2013;Zheng et al, 2016;Huo et al, 2017). Many studies have demonstrated that probiotics can ameliorate these symptoms in rodents , although it should be noted that similar strong evidence is lacking in human probiotic trials, likely due to the complexity of these conditions in humans compared to the relative simplicity of animal models.…”