Original Articles

A randomized, double-blind pilot study of a multi-strain probiotic formulation on depressive symptoms in adults

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Received: 5 December 2025
Published: 29 April 2026
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The gut–brain axis represents a bidirectional communication pathway influencing mood through microbiota-related mechanisms. This randomized, double-blind, active-controlled pilot trial evaluated the effects of a multi-strain Lactobacillus spp. probiotic formulation added to an active control on depressive symptoms in adults with mild-to-moderate depressive symptoms. Sixty participants were randomly assigned to receive either a daily combination containing L. rhamnosus HN001, L. rhamnosus SP1, L. acidophilus LA1, and L. reuteri LR92 (3×10⁹ CFU total) plus L-theanine and Eschscholtzia californica (probiotic group) or an identical active control containing L-theanine and E. californica alone for six weeks. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and the Beck Depression Inventory-II at baseline, week 3, week 6, and after a three-week washout. Significant within-group reductions in depressive symptom scores were observed in the probiotic group, while changes in the active control group were smaller and not statistically significant. However, between-group comparisons did not reach statistical significance at any time point. These findings suggest that the probiotic-containing formulation was associated with improvements in depressive symptoms when administered on top of an active control. Due to the study design, effects cannot be attributed specifically to the probiotic component alone. Larger trials incorporating inert placebo controls and microbiome analyses are warranted.

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CRediT authorship contribution

All authors contributed equally to the present article.

How to Cite



A randomized, double-blind pilot study of a multi-strain probiotic formulation on depressive symptoms in adults. (2026). Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale. https://doi.org/10.4081/jbr.2026.14692