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Background : Accumulating evidence has shown that neuropsychiatric disorders are associated with gut microbiota through the gut-brain axis. However, the effects of antidepressant treatment on gut microbiota are rarely studied. Here, we investigated whether stress led to gut microbiota changes and whether fluoxetine plays a role in microbiota alteration. Methods : We investigated changes in gut microbiota in a depression model induced by chronic unpredicted mild stress (CUMS) and a restoration model by applying the classic antidepressant drug fluoxetine. Results : We found that stress led to low bacterial diversity, simpler bacterial network, and increased abundance of pathogens, such as Escherichia/Shigella , and conditional pathogens, such as Enterococcus , Vagococcus , and Aerococcus. However, these changes were attenuated by fluoxetine directly and indirectly. Furthermore, the correlation analysis indicated strong correlations between gut microbiota and anxiety- and depression-like behaviors. Conclusions : This study revealed that fluoxetine led to restoration of dysbiosis induced by stress stimulation, which may imply a possible pathway through which one CNS target drug plays its role in reshaping the gut microbiota.

Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice