Probiotics and Major Depressive Disorder

December 29, 2022

Two thirds of patients with major depressive disorder (MDD) don’t respond to pharmacological treatment and 30 percent of patients whose medication is optimized still experience residual symptoms. Due to this lack of reliable and effective medical management, other methods should be considered including a focus on the gut-brain axis, which has shown promise for depression.

In this randomized, controlled trial, the effects of short-term, high-dose probiotic add-on therapy for patients with MDD are evaluated. Outcome measures included depression symptoms, gut microbiota composition, and brain structure and function. Participants continued their previously prescribed treatment as usual in addition to a probiotic supplement containing 900 billion CFU/day of a combination of eight different strains over the 4-week study period; the control group received a maltose placebo. Participants were assessed three times: before the intervention, directly after, and again four weeks after the end of the study to evaluate the self-reported depressive symptoms, GI symptoms, and anxiety. Stool samples were collected for DNA extraction to evaluate gut microbiota volume and diversity.

The results showed stronger decreased depression scores in the probiotics group both immediately at the conclusion of the intervention and at the 4-week follow-up. There were no significant changes in the microbial diversity in either group during the study itself. However, at the 4-week follow up, the probiotic group maintained its microbial diversity while the placebo groups’ diversity was significantly reduced. Looking at brain imaging, the probiotic group showed increased grey matter volume in the calcarine sulcus and lingual gyrus, both structures that are involved with processing the visual field, but these changes did not relate to any significant changes in clinical depressive symptoms or the gut microbiome.

While the available literature and evidence is lacking to identify specific probiotic strains that improve depressive symptoms, focusing on easily accessible probiotics is a good course of action for the time being. Future research identifying specific mechanisms of action will be useful to help inform strain-specific strategies to manage depression, other mood disorders, and other conditions affected by the gut.

Note: Iris Wellness center offers a vairety of services and products to support healthy gut Function and optimize the microbial balance of the GI tract.

Contributed by Carly Duffy, MPH, RD


Schaub AC, Schneider E, Vazquez-Castellanos JF, et al. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: A randomized controlled trial. Transl Psychiatry. 2022;12(1):227. doi: 10.1038/s41398-022-01977-z.