Table 2.
Antidepressant efficacy of probiotics assessed by randomized controlled trials.
| Study | Population | Intervention | Control | Treatment detail | Outcome measure | Depressive symptom score changes | Microbiota changes | Gut-brain axis changes |
|---|---|---|---|---|---|---|---|---|
| Akkasheh G et al. 201696 | MDD (N = 40) | Probiotics (N = 20): Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum | Placebo (N = 20): starch | 8 weeks, 2 × 109 CFU/g/day for each species | BDI | Significant decrease in BDI score in probiotic group compared to placebo over 8 weeks. | NA | Serum insulin↓, hs-CRP↓, plasma glutathione↑ |
| Kazemi A et al. 201997 | MDD (N = 110) | Probiotics (N = 38): Lactobacillus helveticus R0052, Bifidobacterium longum R0175 Prebiotics (N = 36): galactooligosaccharide | Placebo (N = 36): excipients | 8 weeks, 10 × 109 CFU/5 g/day | BDI | Significant decrease in BDI score in probiotic group compared to prebiotic and placebo over 8 weeks. | NA | Serum kynurenine/tryptophan ratio↓, tryptophan/isoleucine ratio↑ |
| Messaoudi M et al. 201198 | Health volunteers (N = 55) | Probiotics (N = 26): Lactobacillus helveticus R0052, Bifidobacterium longum R0175 | Placebo (N = 29): excipients | 30 days, 3 × 109 CFU/1.5 g/day | HSCL-90 | Significant decrease in HSCL-90 depression subscore in probiotic group compared to placebo over 30 days. | NA | NA |
| Miyaoka T et al. 201899 | TR-MDD (N = 40) | Probiotics (N = 20): Clostridium butyricum MIY AIRI 588 (CBM588) + antidepressants | Placebo (N = 20): antidepressants | 8 weeks, 60 mg/day | HAMD-17 | Significant decrease in HAMD-17 score in probiotic group compared to placebo over 8 weeks. | NA | NA |
| Schaub AC et al. 2022100 | MDD (N = 60) | Probiotics (N = 30):Streptococcus thermophilus NCIMB 30438, Bifidobacterium breve NCIMB30441, Bifidobacterium longum NCIMB 30435, Bifidobacterium infantis NCIMB 30436, Lactobacillus acidophilus NCIMB 30442, Lactobacillus plantarum NCIMB 30437, Lactobacillus paracasei NCIMB 30439, Lactobacillus delbrueckii subsp.Bulgaricus NCIMB 30440 | Placebo (N = 30): maltose | 4 weeks (31 days), 9 × 1011 CFU/day | HAMD | A significant stronger decrease of HAMD scores in the probiotics compared to the placebo group over 4 weeks | Lactobacillus↑ | Probiotics increase gray matter volume in calcarine sulcus and alter putamen's activation during emotion processing |
| Slykerman RF et al. 2017101 | Pregnancy woman (N = 423) | Probiotics (N = 212): Lactobacillus rhamnosus HN001 | Placebo (N = 211): corn-derived maltodextrin | From enrolment until 6 months postpartum if breastfeeding, 6 × 109 CFU/day | EPDS | Significant lower depression scores in probiotic group compared to placebo from enrolment until 6 months postpartum if breastfeeding | NA | NA |
| Tian P et al. 2022102 | MDD (N = 51) | Probiotics (N = 25): Bifidobacterium breve CCFM1025 | Placebo (N = 26): maltodextrin | 4 weeks, 1 × 1010 CFU/day | HDRS-24 | Significant decrease in HDRS-24 score in probiotic group compared to placebo over 4 weeks | Desulfovibrio↑, Faecalibaculum↑ | Serum 5-HIAA↓ |
| Zhang X et al. 2021103 | MDD with constipation (N = 82) | Probiotics (N = 41): Lacticaseibacillus paracaseiYIT 9029 | Placebo (N = 41) | 9 weeks, 1.0 × 1010 CFU/day | BDI | Significant decrease in BDI score in probiotic group over 9 weeks. | Veillonella↑, Neisseria↑, Ralstonia↑, Eggerthella↑, Rikenellaceae_RC9_gut_group↓, Sutterella↓, Oscillibacter↓, Rothia ↓ | Serum IL-1β↓, IL-6↓, and TNF-α↓ |
Notes: MDD, Major depressive disorder; TR-MDD, Treatment-resistant major depressive disorder; CFU, Colony forming units; BDI, Beck Depression Inventory; HSCL-90, Hopkins Symptom Checklist-90; HAMD, Hamilton Depression Rating Scale; EPDS, Edinburgh Postnatal Depression Scale; HDRS-24, Hamilton Depression Rating scale-24; hs-CRP, Hypersensitive c-reactive protein; 5-HIAA, 5-Hydroxyindole-3-acetic acid; IL-1β, Interleukin-1β; IL-6, Interleukin-6; TNF-α, Tumor necrosis factor-α.
NA represents no data.