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• The transcriptome characteristics of CSDS were more focused on neuronal and synapse. • The transcriptome characteristics of FMT were more focused on inflammation. • The common transcriptome characteristics of two models was energy metabolism. • The CSDS had large more alternative splicing events than FMT. Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression. [ABSTRACT FROM AUTHOR]