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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-021-05958-w.