Metabolomics changes in brain-gut axis after unpredictable chronic mild stress

Abstract

Abstract Background Major depressive disorder is a leading cause of disability worldwide, affecting up to 17 % of the general population. The neural mechanisms of depression, however, are yet to be uncovered. Recently, attention has been drawn to the effects of dysfunctional brain-gut axis on depression, and many substances have been suggested to be involved in the communication between the gut and brain, such as ghrelin. Methods We herein systematically examined the changes of metabolomics after unpredictable chronic mild stress (UCMS)–induced depression-like behaviors in rats and compared the altered metabolites in the hippocampus and jejunum samples. Results Our results show that many metabolites significantly changed with UCMS both in the hippocampus and jejunum, such as L-glutamine, L-tyrosine, hydroxylamine, and 3-phosphoglyceric acid. Further studies suggested that these changes are the reasons for anxiety-like behaviors and depression-like behaviors in UCMS rats and also are the reasons for hippocampal neural plasticity. Conclusions Coexistence of brain and gut metabolic changes in UCMS-induced depressive behavior in rats suggests a possible role of brain-gut axis in depression. This study provides insights into the neurobiology of depression.