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.

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.

We consider a self-interacting dark matter model in which the massive dark photon mediating the selfinteraction decays to light dark fermions to avoid over-closing the universe. We find that if the model is constrained to explain the dark matter halos inferred for spiral galaxies and galaxy clusters simultaneously, there is a strong indication that dark matter is produced asymmetrically in the early universe. It also implies the presence of dark radiation, late kinetic decoupling for dark matter, and a suppressed linear power spectrum due to dark acoustic damping. The Lyman-α forest power spectrum measurements put a strong upper limit on the damping scale and the model has little room to reduce the abundances of satellite galaxies. Future observations in the matter power spectrum and the CMB, in tandem with the impact of self-interactions in galactic halos, makes it possible to measure the gauge coupling and masses of the dark sector particles even when signals in conventional dark matter searches are absent.