Possible role of the gut microbiota in the antidepressant effects of fluoxetine in a chronic unpredicted mild stress model

Fluoxetine is the most widely used antidepressant drug worldwide, recently accumulating evidence suggests that gut microbiota play a key role in the pathogenesis of depression, and the antidepressant actions of certain compounds are related to the alteration of gut microbiota. Here, we investigated whether fluoxetine treatment lead to gut microbiota changes, and whether the gut microbiota plays a role in the antidepressant effects of fluoxetine. We found that chronic unpredicted mild stress(CUMS) lead to low bacterial diversity, increased abundance of Bacteroides, Escherichia/Shigella, Enterococcus, Romboutsia, Staphylococcus, Vagococcus, Enterorhabdus and Aerococcus, decreased abundance of Parasutterella, However, all these alteration was corrected by fluoxetine. Furthermore, the altered bacteria were associated with depression-like behaviors. In conclusion, this study suggests that the antidepressant effects of fluoxetine in CUMS model may be partly mediated by the restoration of the gut microbiota. Most intriguingly, the specific of fluoxetine on the bacterial diversity, Escherichia/Shigella and Enterorhabdus may explain its antidepressant action.