Antibiotics-induced depression in mice via the microbiota-gut-brain axis.

Background: Intestinal dysbacteriosis is associated with depression. This study aimed to establish an antibiotics-induced depression mouse model and explore the mechanism of antibiotic-induced depression.

Methods: C57BL/6 J mice were treated with antibiotics to prepare the antibiotic-induced depression mouse model. Behavioral tests and depression-related bio-markers were examined. To understand the abundance of different bacteria in intestinal flora and screen out the predominant bacterial species, metagenomic analysis of feces was carried out. Finally, we detected the expression of NF-κB-p65 and p-NF-κB-p65 in PFC and the hippocampus using Western blot.

Results: Mixtures A and B caused depression-like behavior in mice. Norepinephrine, 5-hydroxytryptamine, and brain-derived neurotrophic factor in hippocampus and PFC of antibiotic-induced depression mice significantly decreased. The serum adrenocorticotropic hormone and corticosterone concentrations increased. The abundance values of Bacteroides thetaiotaomicron, Klebsiella oxytoca, and Klebsiella aerogenes in antibiotic-induced depression mice significantly increased, and the characteristic KO genes and metabolic pathways in antibiotic-induced depression mice were significantly different with in CUMS depression mice (the positive control) and normal mice. The relative levels of p-NF-κB-p65 in antibiotics-induced depression mice were significantly higher than in normal mice.

Limitations: How dysbacteriosis induces inflammation in the central nervous system is unclear.

Conclusions: Specific antibiotic mixture can cause depression-like behavior and changes of depression-related bio-markers in mice. The antibiotic-induced depression mice display changes in the species and metabolism of intestinal bacterial flora. The activation of NF-κB inflammatory signaling pathway in the central nervous system may act as one of the mechanisms in the development of antibiotic-induced depression.