Table 5.
Major findings in the clinical trials on prebiotics, probiotics and synbiotics in major depressive disorder included in the systematic review.
| Authors | Population | Intervention | Control | Trial Length | Outcome Measure | Depressive Symptom Score Changes | Microbiome Changes |
|---|---|---|---|---|---|---|---|
| Akkasheh 2016 [70] | MDD (N = 40) |
L. acidophilus, L. casei, B. bifidum | Plb | 8 weeks | BDI | Significant decrease in BDI score in probiotic group compared to placebo over 8 weeks. | ND |
| Bambling 2017 [71] | Resistant MDD (N = 12) |
Mg2+, L. acidophilus, B. bifidum, S. thermophiles | No ctr | 8 weeks 8, 16-wk f/u |
BDI | Significant decrease in BDI score in probiotic group over 8 weeks, but not at 16 weeks. | ND |
| Romijn 2017 [72] | Low mood (N = 79) |
L. helveticus R0052, B. longum R0174 | Matched Plb | 8 weeks | MADRS | No significant difference in MADRS score in probiotic group compared to placebo over 8 weeks. | ND |
| Ghorbani 2018 [73] | MDD (N = 40) |
Familact H® a Syn, Fluoxetine | Plb, Fluoxetine | 8 weeks | HAMD-17 | Significant decrease in HAMD-17 score in synbiotic group compared to placebo over 8 weeks. | ND |
| Miyaoka 2018 [74] | TRD (N = 40) |
C. butyricum miyairi 588, Antidepressants | Anti-depressants | 6 weeks | HAMD-17, BDI | Significant decrease in HAMD-17 and BDI score in probiotic group compared to control over 6 weeks. | ND |
| Chahwan 2019 [77] | Clinical and sub-clinical depression (N = 71) | Ecologic®Barrier c | Plb Ctr |
8 weeks | BDI | No significant difference in BDI score between probiotic group and placebo over 8 weeks. | No significant differences in α-diversity or β-diversity between probiotic and placebo groups over time. |
| Kazemi 2019 [75] | MDD (N = 110) |
CEREBIOME® b | Plb | 8 weeks | BDI | Significant decrease in BDI score in probiotic group compared to placebo or prebiotic over 8 weeks. No significant decrease in prebiotic group BDI score compared to placebo over 8 weeks. | ND |
| Rudzki 2019 [76] | MDD (N = 60) |
L. Plantarum 299v, SSRI | Plb + SSRI | 8 weeks | HAMD-17 | No significant difference in HAMD-17 score between probiotic group and placebo over 8 weeks. | ND |
| Heidarzadeh 2020 [79] | MDD (N = 78) |
CEREBIOME® b | Plb | 8 weeks | BDI-II | Significant decrease in BDI-II score in probiotic compared to placebo over 8 weeks. No significant difference in BDI-11 score between probiotic and prebiotic, or prebiotic and placebo groups over 8 weeks. | ND |
| Reininghaus 2020 [80] | MDD (N = 82) |
OMNi-BiOTiC® Stress Repair d | Plb (Biotin, B7) | 4 weeks | HAM-D, BDI-II |
No significant decrease in HAM-D and BDI-II score in probiotic group compared to placebo over 4 weeks. | No significant differences in α-diversity between probiotic and placebo groups over time. β-diversity was significantly different in the probiotics group after 28 days. Increased Ruminococcus gauvreauii and Coprococcus 3 abundance in Pro after 28 days. |
| Reiter 2020 [81] | MDD (N = 61) |
OMNi-BiOTiC® Stress Repair d, Biotin | Plb (Biotin, B7) | 4 weeks | HAM-D, BDI-II |
No significant decrease in HAM-D and BDI-II score in probiotic group compared to placebo over 4 weeks. | ND |
| Saccarello 2020 [82] | MDD (N = 90) |
SAMe, L. plantarum HEAL9 | Plb | 6 weeks 2,6-wk f/u |
Z-SDS | Significant decrease in Z-SDS score in probiotic group compared to placebo at week 2 and 6. | ND |
| Arifdjanova 2021 [87] | Mild-moderate depressive episode | Bac-Set-Forte e | Plb | 6 weeks | HAMD-17 | Significant decrease in HAMD-17 score in probiotic group compared to placebo over 6 weeks. | ND |
| Browne 2021 [83] | Depressive sxs (N = 40) |
Ecologic®Barrier c | Plb | 8 weeks | EPDS | No significant decrease in EDPS score in probiotic group compared to placebo over 8 weeks. | ND |
| Chen 2021 [84] | MDD (N = 11) |
L. plantarum PS128 | None | 8 weeks | HAMD-17 | Significant decrease in HAMD-17 score in probiotic group over 8 weeks. | No significant differences in α-diversity and β-diversity in probiotic group over 8 weeks. |
| Vaghef-Mehrabany 2021 [78] | MDD (N = 62) |
Inulin 10 g/day | Plb (Maltodextrin 10 g/day) |
8 weeks | HAM-D BDI-II |
No significant difference in HAM-D and BDI-II score in prebiotic group compared to placebo over 8 weeks. | |
| Wallace 2021 [53] | MDD (N = 10) |
CEREBIOME® b | No ctr | 8 weeks | MADRS | Significant decrease in MADRS score in probiotic group between baseline and 4 weeks. No significant decrease between 4 weeks and 8 weeks. | ND |
| Zhang 2021 [86] | MDD (N = 69) |
L. casei Shirota | Plb | 9 weeks | BDI, HAM-D | No significant decrease in HAM-D score in probiotic group compared to placebo over 9 weeks. | No significant differences in α-diversity and β-diversity between probiotic and placebo groups over 9 weeks. Increased Adlercreutzia, Megasphaera and Veillonella and decreased Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter in probiotic compared to placebo over 9 weeks. |
| Tian 2022 [85] | MDD (N = 45) |
B. breve CCFM1025 | Plb (Maltodextrin) | 4 weeks | HAMD-17 | Significant decrease in HAMD-17 score in probiotic group compared to placebo over 4 weeks. | Significant difference in α-diversity between probiotic and placebo according to Chao 1 index and observed operational taxonomic units (OTUs) but not the Shannon index. No significant difference in β-diversity. Increased Desulfovibrio, Faecalibacterium and Bifidobacterium in probiotic compared to placebo over 4 weeks. |
Note. Abbreviations: BDI, Beck Depression Inventory; BDI-II, Beck Depression Inventory-II; CES-D, Center for Epidemiological Studies Depression Scale; Ctr, control; DASS-42-D, depression subscale of the Depression, Anxiety and Stress Scale; F/u, follow up; HAM-D, Hamilton Depression Rating Scale; HAMD-17, Hamilton Depression Rating Scale-17; MADRS, Montgomery-Asberg Depression Rating Scale; MDD, major depressive disorder; ND, Not declared; Plb, placebo; Pre, prebiotic; Pro, probiotic; RCT, Randomized controlled trial; Ref, Reference; SAMe, S-adenosylmethionine; SSRI, Selective Serotonin Reuptake Inhibitor; Syn, synbiotic; Z-SDS, Zhung Self-rating Depression Scale. a Familact H® synbiotic consists of L. casaei, L. acidofilus, L. bulgarigus, L. rhamnosus, B. breve, B. longum, and S. thermophilus. b CEREBIOME® consists of L. helveticus R0052 and B. longum R0175. c Ecologic®Barrier consists of B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19 and L. lactis W58. d OMNi-BiOTiC® Stress Repair consists of B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W22, L. casei W56, L. paracasei W20, L. plantarum W62, L. salivarius W24 and L. lactis W19. e Bac-Set-Forte consists of S. thermophilus, B. infantis, B. bifidum, B. breve; B. longum, L. delbrueckii, L. bulgaricus, L. helveticus, L. salivarius, L. fermentum, L. casei, L. plantarum, L. rhamnosus, L. acidophilus, and L. lactis.