TABLE 1.

Clinical studies investigating a correlation between the human fecal microbiota and depression.

References	Sample	Sample size (patients/controls)	Mean age in years ± SD	Gender (males/females)	Changes in taxonomic composition in patients	Limitations/notes
Naseribafrouei et al., 2014	Fecal sample	55 Patients: 37 Controls: 18	Patients: 49.2 ± 13.9 Controls: 46.1 ± 13.9	Patients: (17/20) Controls: (7/11)	-High taxonomic level: ↑Bacteroidales ↓Lachnospiraceae -Low taxonomic level: ↑correlating OTUs of clades within the genus Alistipes and Oscillibacter	- A lack of data on the dietary habits of subjects - A small cohort with a risk of overseeing effects
Jiang et al., 2015	Fecal sample	76 Active-MDD: 29 Responded-MDD: 17 Controls: 30	Patients: Active-MDD: 25.3 ± 5.4 Responded-MDD: 27.1 ± 5.4 Controls: 26.8 ± 5.4	Patients: Active-MDD: (18/11) Responded-MDD: (9/8) Controls: (15/15)	-High taxonomic level: ↑Bacteroidete ↑Proteobacteria ↑Actinobacteria ↓Firmicutes -Low taxonomic level: ↑Enterobacteriaceae ↑Alistipes ↓Faecalibacterium	- A lack of data on the dietary habits of subjects - Possible effects of atypical antipsychotic medications - Further studies are required to evaluate the suitability of the microbiome as a biomarker.
Zheng et al., 2016	Fecal sample	121 Drug-naïve MDD: 39 Treated-MDD: 19 Controls: 63	Patients: 40.6 ± 11.7 Controls: 41.8 ± 12.3	Patients: (22/36) Controls: (23/40)	-High taxonomic level: ↑Actinobacteria ↓Bacteroidetes -Low taxonomic level: ↑OUTs assigned to the families Actinomycineae, Coriobacterineae, Lactobacillaceae, Streptococcaceae, Clostridiales incertae sedis XI (Parvimonas), Eubacteriaceae, Lachnospiraceae (Anaerostipes, Blautia, Dorea, Lachnospiracea incertae sedis), Ruminococcaceae (Clostridium IV) and Erysipelotrichaceae incertae sedis ↓OUTs assigned to the families Bacteroidaceae, Rikenellaceae (Alistipes), Lachnospiraceae (Coprococcus, Clostridium XlVa, Lachnospiraceae incertae sedis, Roseburia and Faecalibacterium), Acidaminococcaceae (Phascolarctobacterium), Veillonellaceae(Megamonas) and Sutterellaceae	- No examination of other neuropsychiatric disorders with similar clinical presentations to MDD - A possibility of site-specific and ethnic biases in microbial phenotypes
Aizawa et al., 2016	Fecal sample	100 Patients: 43 Controls: 57	Patients: 39.4 ± 10.0 Controls: 42.8 ± 12.7	Patients: (25/18) Controls: (22/35)	↓Bifidobacterium A tendency of ↓Lactobacillus	- Investigating only Bifidobacterium and Lactobacillus -Possible effects of antidepressant medications - Effects of diet were not fully taken into account in the analysis.
Chen Z. et al., 2018	Fecal sample	20 Patients: 10 Controls: 10	Patients: 43.9 ± 13.8 Controls: 39.6 ± 9.0	Patients: (5/5) Controls: (5/5)	-High taxonomic level: ↑Firmicutes ↑Actinobacteria ↓Bacteroidetes ↓Proteobacteria -Low taxonomic level: ↑Lachnospiraceae ↑Actinomycetaceae ↑Nocardiaceae ↑Bifidobacteriaceae ↑Erysipelotrichaceae ↑Clostridiaceae ↑Ruminococcaceae ↑Porphyromonadaceae ↑Streptomycetaceae ↓Enterobacteriaceae ↓Sutterellaceae ↓Oscillospiraceae ↓Chitinophagaceae ↓Marinilabiliaceae ↓Rikenellaceae ↓Prevotellaceae	- A limited sample size - No detailed data on diet habits, alcohol intake, or residence - Possible effects of antidepressant medications
Chung et al., 2019	Fecal sample	73 Patients: 36 Controls: 37	Patients: 45.83 ± 14.08 Controls: 41.19 ± 12.73	Patients: (8/28) Controls: (14/23)	-High taxonomic level: ↑Actinobacteria ↑Firmicutes ↓Bacteroidetes ↓Proteobacteria -Low taxonomic level: ↑Peptostreptococcaceae ↑Porphyromonadaceae ↑Streptococcaceae ↑Bifidobacteriaceae ↑Lachnospiraceae ↓Prevotellaceae ↓Alcaligenaceae	- A cross-sectional study design with no causal inference between the microbiota alterations and depression - A moderate sample size that provided no stable results with cluster analysis to further discuss the impacts of dietary patterns on microbiota compositions - Possible effects of antidepressant medications -The dietary information was subjective to recall bias.

↑indicates an increase; ↓ indicates a decrease; MDD, Major depressive disorder; OTUs, Operational Taxonomic Units.