Depression Can Be Transmitted via Gut Microbiota and Induce Liver Metabolic Disorders and Brain Inflammation

Abstract

Background: Generally, depression is caused by a deficiency in the monoamine transmitters of the brain, norepinephrine (NE) and serotonin (5-HT). Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiota contribute to the process of depression and further influence of the host Methods: Fecal microbiota transplant (FMT) is applied to illustrate depression can be transmitted via microbiota and metabolism and serum analysis are applied to demonstrate further influence to the liver and the brain. Findings: Depression-like behavior is observed after antibiotic-treated rats colonize gut microbiota derived from chronic unpredictable mild stress (CUMS) rats, which corresponds to a decrease in 5-HT expression in plasma. Moreover, increased Zonulin and Fatty Acid Binding Protein-2 (FABP2) in the plasma indicate that gut barrier integrity is broken in FMT rats. Since the liver receives blood from the intestines and metabolizes the products of the gut microbiota, liver metabolic disorder occurs after FMT. LC-MS shows that changed metabolites were mainly assigned to 'energy metabolism', 'lipid metabolism' and 'acid metabolism' categories. In addition, increased inflammatory cytokines expression and higher astrocytes activation in the hippocampus indicating inflammatory process in the brain after FMT. Interpretation: These findings suggest that disturbance of the gut microbiota contribute to pathogenesis of depression and further cause liver metabolic disorders and brain inflammation. Funding Statement: This work was supported by the National Natural Science Foundation of China (NO. 31472232) and the Department of Agriculture of Guangdong Province, the Project of SCAU TCVM Training Base. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the Southern Medical University Experimental Animal Ethics Committee. All experimental procedures were performed in accordance with the relevant guidelines approved by the Experimental Animal Ethics Committee of Southern Medical University.