The relationship between “microbiota-gut-brain” axis and depression: Chronic stress-induced inflammation

Abstract

This study aims to investigate the pathogenesis of depression in mice using the chronic unpredictable mild stress (CUMS) model, with a particular focus on the changes in inflammatory gene networks and inflammatory factor levels under the condition of gut microbiota dysbiosis. The results indicate that CUMS-induced mice exhibited significant depressive-like behaviors. Specifically, they displayed reduced sucrose intake in the sucrose preference test, decreased central area distance and time in the open field test, and reduced percentage of entries and time spent in the open arm in the elevated plus maze test. Molecular biological analysis indicated that CUMS treatment significantly upregulated the levels of inflammatory factors TNF-α, IL-1β, IL-6, and IFN-γ in the serum and hippocampus of mice. Through high-throughput sequencing and Pearson correlation analysis, it was found that the levels of inflammatory factors were significantly positively correlated with the expression of multiple inflammatory pathway genes, as well as the abundance of beneficial and harmful bacteria. Furthermore, the persistent changes in inflammatory factors ultimately led to neuronal cell death. This study provides strong evidence for the role of disrupted “microbiota-gut-brain” axis homeostasis in the pathogenesis of CUMS-induced depression in mice. This finding offers a new perspective for understanding the pathological mechanisms of depression and provides strategies for future depression treatment.