TOPLINE

Treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) was associated with a reduced abundance of Clostridium sensu stricto 1 in patients with major depressive disorder (MDD).

METHODOLOGY

• Researchers conducted cross-sectional analyses in two independent cohorts from Germany (MACS cohort) and the Netherlands (MIND-Set cohort) to test whether antidepressant treatment altered gut microbiome composition in patients with MDD.
• They included 1802 participants, comprising 924 patients with MDD (mean age, 37.1-42.0 years) and 878 unaffected control individuals (mean age, 35.7-39.0 years).
• Among patients with MDD, 394 were treated with SSRIs or SNRIs (with or without other psychotropic medications), 147 used only other psychotropic medications, and 383 were unmedicated.
• Gut microbiome composition was assessed using 16S ribosomal RNA gene sequencing from fecal samples, with taxonomic analysis performed at the genus level.
• Researchers first identified microbial genera associated with MDD diagnosis in the MACS cohort, then tested whether these genera were also associated with SSRI/SNRI treatment in both cohorts, followed by meta-analysis across cohorts.

TAKEAWAY

• Nine genera showed significant associations with MDD diagnosis in the MACS cohort, including elevated abundance of Hungatella and Eggerthella, and reduced abundance of Clostridium sensu stricto 1 and Lachnospiraceae FCS020 group.
• Meta-analysis across both cohorts revealed a significant negative association between SSRI/SNRI treatment and abundance of Clostridium sensu stricto 1.
• The association with Clostridium sensu stricto 1 was specific to SSRI/SNRI treatment and not observed with other psychotropic medications when compared with unmedicated patients.
• The reduced Clostridium sensu stricto 1 abundance in patients with MDD vs controls was driven by SSRI/SNRI treatment status, with stronger associations and larger effect sizes in the SSRI/SNRI-treated group than the unmedicated group.

IN PRACTICE

"[The] findings clarify the drivers of microbial alterations in depression and lay the groundwork for microbiome-targeted interventions to improve treatment outcomes in MDD [major depressive disorder]," the authors of the study wrote.

SOURCE

The study was led by Eugenia Emile Natasha, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands. It was published online on July 16 in Communications Medicine.

LIMITATIONS

Researchers could not determine whether microbiome changes were acute or chronic or link them to symptom trajectories owing to limited data. Small, imbalanced subgroups of individual antidepressants precluded reliable assessment of compound‑specific effects. Reliance on fecal samples may not have captured drug-microbiome interactions in the small intestine.

DISCLOSURES

The study received funding from the European Union's Horizon Europe research and innovation programme under a Marie Curie Postdoctoral Fellowship and the Brain & Behavior Research Foundation Young Investigator Grant. Additional funding was provided by the German Research Foundation and other organizations to multiple authors. Several authors reported grants, personal fees, or research support from various pharmaceutical companies and other organizations. Detailed author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.