Interaction Between the Intestinal Microbial Structure and Function Dysbiosis and Hippocampal Transcriptome Profile for Anxiety-like Induced by Doxorubicin in Mice.

BACKGROUND:Cancer patients can have psychological disorders such as anxiety after chemotherapy, which severely influence their quality of life. OBJECTIVE:In this study, we aimed to explore the relationship between the gene expression level and the gut microbiota composition/function for anxiety-like behavior induced by doxorubicin. METHODS:C57BL/6J mice were intraperitoneally injected with 2.5 mg/kg doxorubicin once a week for 4 weeks and constructed a mouse model that mice transplanted fecal microbiota of doxorubicin-treated mice. The elevated Plus Maze (EPM) and Open Field Test (OFT) assessed anxiety-like behaviors. 16S rRNA gene sequencing of fecal samples was used to explore the intestinal microbial structure and function. RNA-sequencing of the hippocampus explored the underlying mechanisms and transcriptional changes. RESULTS:Treatment with doxorubicin and fecal microbiota transplantation (FMT) produced anxiety-like behavior in mice. 16S rRNA fecal sequencing revealed differences in microbial composition between the vehicle groups (Veh) and doxorubicin groups (Dox). COG analyses showed that the Dox mice displayed decreased clusters of Carbohydrate transport and metabolism, transcription, signal transduction mechanism and defense mechanisms from the Veh mice. RNA-sequencing analysis showed that the 22 significantly differentially expressed genes DEGs. Spearman correlation analysis indicated 22 DEGs were associated with the different bacteria flora between the two groups. CONCLUSION:Overall, our data illustrated that the intestinal microbial structure and function dysbiosis is associated with the anxiety-like behavior induced by doxorubicin and hippocampal gene expression. And supported the microbiota regulation as a therapeutic approach for the treatment of neurogenic disease.