Key PointsQuestionAre probiotics an acceptable, tolerable, and potentially efficacious adjunctive treatment for depression?FindingsIn this pilot randomized clinical trial including 49 participants, daily probiotic intake for 8 weeks resulted in greater improvements in depressive and anxiety symptoms compared with placebo.MeaningThe acceptability, tolerability, and estimated effect sizes on key clinical outcomes are promising and encourage further investigation of probiotics as adjunctive treatment for people with major depressive disorder in a definitive efficacy trial.