Exploring the mechanisms of action of probiotics in depression: Results from a randomized controlled pilot trial

TY - JOUR

T1 - Exploring the mechanisms of action of probiotics in depression

T2 - Results from a randomized controlled pilot trial

AU - Nikolova, Viktoriya L

AU - Cleare, Anthony J

AU - Young, Allan H

AU - Stone, James M

N1 - Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2025/5/1

Y1 - 2025/5/1

N2 - BACKGROUND: We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects.METHODS: 49 people with MDD received a multi-strain probiotic (n = 24) or placebo (n = 25) for 8 weeks in addition to their antidepressant. Stool and blood samples were collected to analyse gut microbiota composition and inflammatory cytokines. Stool samples from 25 matched healthy volunteers (HVs) were also obtained.RESULTS: Within the probiotic group, there was a significant increase in richness according to Chao1(bias-corrected) (w4 p = 0.04) and a trend for increased Total count (w4 p = 0.06, w8 p = 0.09) compared to baseline, but not to placebo. When compared to HVs post-treatment, only the placebo group had a significant decrease in Shannon' entropy (p = 0.03) and a trend for decreased Total count (p = 0.08) and Simpson's index (p = 0.09). Between-group differences in beta diversity were observed at week 4 (p = 0.04), but not week 8. Consistent between-group differences were seen in family Bacilleceae post-treatment (FDR p < 0.05), which correlated with decreases in anxiety (FDR p < 0.05). There were no differences in inflammatory markers.LIMITATIONS: This study was limited by data loss during the COVID-19 Pandemic.CONCLUSION: Probiotics may positively impact the microbiota by normalising diversity and increasing levels of health-related taxa, which may partially account for their benefits in MDD. Understanding how these changes relate to symptom improvement can inform their targeted use in clinical practice. Larger trials incorporating functional multi-omics are needed.TRIAL REGISTRATION: NCT03893162.

AB - BACKGROUND: We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects.METHODS: 49 people with MDD received a multi-strain probiotic (n = 24) or placebo (n = 25) for 8 weeks in addition to their antidepressant. Stool and blood samples were collected to analyse gut microbiota composition and inflammatory cytokines. Stool samples from 25 matched healthy volunteers (HVs) were also obtained.RESULTS: Within the probiotic group, there was a significant increase in richness according to Chao1(bias-corrected) (w4 p = 0.04) and a trend for increased Total count (w4 p = 0.06, w8 p = 0.09) compared to baseline, but not to placebo. When compared to HVs post-treatment, only the placebo group had a significant decrease in Shannon' entropy (p = 0.03) and a trend for decreased Total count (p = 0.08) and Simpson's index (p = 0.09). Between-group differences in beta diversity were observed at week 4 (p = 0.04), but not week 8. Consistent between-group differences were seen in family Bacilleceae post-treatment (FDR p < 0.05), which correlated with decreases in anxiety (FDR p < 0.05). There were no differences in inflammatory markers.LIMITATIONS: This study was limited by data loss during the COVID-19 Pandemic.CONCLUSION: Probiotics may positively impact the microbiota by normalising diversity and increasing levels of health-related taxa, which may partially account for their benefits in MDD. Understanding how these changes relate to symptom improvement can inform their targeted use in clinical practice. Larger trials incorporating functional multi-omics are needed.TRIAL REGISTRATION: NCT03893162.

UR - http://www.scopus.com/inward/record.url?scp=85217139687&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2025.01.153

DO - 10.1016/j.jad.2025.01.153

M3 - Article

C2 - 39924003

SN - 0165-0327

VL - 376

SP - 241

EP - 250

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -