The effect of SSRI/SNRI antidepressant treatment on the gut microbiota of patients with major depressive disorder

The gut microbiome has been linked to major depressive disorder (MDD), yet it remains unclear whether antidepressant treatment influences these associations. This study aimed to clarify the role of serotonin reuptake inhibitors (SSRI/SNRI) in shaping gut microbiome changes observed in MDD. We conducted cross-sectional analyses in two independent patient cohorts (total N = 1802) and a meta-analysis across both cohorts, comparing the gut microbiome of MDD patients with and without SSRI/SNRI treatment. SSRI/SNRI use was consistently associated with reduced Clostridium sensu stricto 1 abundance. This effect was specific to SSRI/SNRI treatment and not observed with other psychotropic medications. Importantly, reductions in Clostridium sensu stricto 1 in MDD compared to unaffected controls were explained by SSRI/SNRI medication status. Here, we show that antidepressant treatment is an important factor shaping gut microbiome alterations linked to MDD, underscoring the need to account for medication effects and potentially informing future microbiome-based strategies to improve treatment response.