. 2023 Apr 4;2(2):e99. doi: 10.1002/imt2.99

Table 1.

Summary of schizophrenia‐related gut microbial alterations reported in clinical studies.

Author (Year)	Study design	Population characteristics	Intervention	Clinical findings (vs. HCs)
Evidence for: Low‐grade inflammation mediated by gut microbial dysbiosis
Zheng et al. (2019) [42]	Cross‐sectional study Fecal samples 16S rRNA sequencing	Chinese population: 63 SZ, 69 HCs Female: 33%, 48% Age (years): 43.49 ± 1.68, 39.99 ± 1.62 BMI (kg/m²): 22.90 ± 0.32, 23.16 ± 0.33 Illness duration (N/A) Antipsychotics (58 SZ)	N/A	Microbial α‐diversity ↓ Veillonellaceae and PANSS scores (−) Lachnospiraceae and PANSS scores (+) Microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) for discriminating SZ from HCs (ROC = 0.769)
Zhang et al. (2020) [43]	Cross‐sectional study Fecal samples 16S rRNA sequencing	Chinese population: 10 FSZ, 16 HCs Female: 40%, 44% Age (years): 37.6 ± 7.2, 35.8 ± 6.8 BMI (kg/m²): 23.3 ± 6.8, 22.3 ± 6.5	N/A	Microbial α‐diversity ↓ Phylum: Proteobacteria ↑ Genus: Faecalibacterium and Lachnospiraceae ↓
Li et al. (2020) [44]	Cross‐sectional study Fecal samples 16S rRNA sequencing	Chinese population: 82 SZ, 80 HCs Female: 44%, 51% Age (years): 42.15 ± 13.13, 41.03 ± 14.34 BMI (kg/m²): 24.48 ± 4.33, 23.03 ± 3.05 Illness duration (N/A) Antipsychotics (75 SZ)	N/A	Microbial α‐diversity (ns) Phylum: Actinobacteria ↑; Firmicutes ↓ Genus: Collinsella, Lactobacillus, Succinivibrio, Mogibacterium, Corynebacterium ↑; Adlercreutzia, Anaerostipes, Ruminococcus and Faecalibacterium ↓. Succinivibrio and PANSS scores (+) Corynebacterium and PANSS scores (−)
Xu et al. (2020) [45]	Cross‐sectional study Fecal samples Shotgun sequencing 16S rRNA sequencing	Chinese population: Discovery: 40 SZ, 40 HCs Female: 50%, 50%. BMI: N/A Age (years): 35 ± 11, 34 ± 9 Validation: 44 SZ, 44 HCs Female: 36%, 36% Age (years): 35 ± 11, 35 ± 11 BMI (kg/m²): 22.0 ± 3.2, 23.1 ± 3.7 Illness duration (N/A) Antipsychotics (N/A)	N/A	Microbial α‐diversity ↓ Phylum: Actinobacteria ↑ Genus: Eggerthella and Megasphaera ↑; Enterococcus ↓ Species: Akkermansia muciniphila, Bifidobacterium adolescentis, Clostridium perfringens, Lactobacillus gasseri and Megasphaera elsdeniis↑
Shen et al. (2018) [46]	Cross‐sectional study Fecal samples 16S rRNA sequencing	Chinese population: 64 SZ, 53 HCs Female: 44%, 34% Age (years): 42 ± 11, 39 ± 14 BMI (kg/m²): 23.49 ± 3.8, 23.14 ± 2.8 Illness duration ≤ 10 years Antipsychotics >6 months	N/A	Microbial α‐diversity (ns) Phylum: Proteobacteria ↑ Genus: Succinivibrio, Megasphaera, Collinsella, Clostridium, Klebsiella, Methanobrevibacter ↑; Blautia, Coprococcus, Roseburia ↓. Microbial panel discriminating SZ from HCs (ROC = 0.837)
Schwarz et al. (2018) [48]	Cross‐sectional and 12 month follow‐up Fecal samples Shotgun sequencing	Finnish population: 28 FEP, 16 HCs Female: 43%, 50% Age (years): 25.9 ± 5.5, 27.8 ± 6.0 BMI (kg/m²): 23.8 ± 4.3, 23.9 ± 3.1	N/A	Genus: Lactobacillus, Tropheryma, Halothiobacillus, Saccharophagus, Ochrobactrum, Deferribacter and Halorubrum ↑; Anabaena, Nitrosospira, Gallionella, Bacteroides, Ruminococcus, and Faecalibacterium ↓ Lactobacillus and psychotic symptoms (+) Lactobacillus and treatment response (−) (up to 12 months)
Zhang et al. (2018) [49]	Cross‐sectional study Fecal samples 16S rRNA sequencing	Chinese population: 12 aSZ, 13 rSZ Female: 50%, 46% Age (years): 36.5 ± 8.9, 36.2 ± 8.2 BMI (kg/m²): 23.7 ± 3.2, 24.2 ± 2.7 Duration (years): 8.0 ± 6.9, 9.3 ± 6.4 Antipsychotics >6 months	N/A	aSZ (vs. rSZ): Microbial α‐diversity ↓ Genus: Bacteroides ↑, Prevotella ↓ Genus Prevotella and PANSS scores (−)
Evidence against: Low‐grade inflammation mediated by gut microbial dysbiosis
Nguyen et al. (2018) [41]	Cross‐sectional study Fecal samples 16S rRNA sequencing	American population: 25 SZ, 25 HCs Female: 40%, 44% Age (years): 52.9 ± 11.2, 54.7 ± 10.7 BMI (kg/m²): 31.8 ± 5.4, 28.9 ± 4.0 Illness duration >10 years Antipsychotics (21 SZ)	N/A	Microbial α‐diversity (ns) Phylum: Proteobacteria ↓ Genus: Anaerococcus ↑; Haemophilus, Sutterella, Clostridium ↓. Family Ruminococcaceae and Negative symptoms (−)
Ma et al. (2020) [50]	Cross‐sectional study Fecal samples 16S rRNA sequencing	Chinese population: (40 FSZ, 85 TSZ), 69 HCs Female: 46%, 46% Age (years): 24.19 ± 6.18, 23.14 ± 3.20 BMI: 18–25 kg/m² Antipsychotics (TSZ) > 3 months Illness duration (TSZ) > 1 year	N/A	FSZ (vs. HCs): Microbial α‐diversity (ns) Genus: Actinobacillus, Fusobacterium, Megasphaera, SMB53 ↓; Escherichia ↑ TSZ (vs. FSZ and HCs): Microbial α‐diversity ↓ Genus: Escherichia, Enterococcus, Lactobacillus, Shigella, Streptococcus ↑

Author (Year)

Study design

Population characteristics

Intervention

Clinical findings (vs. HCs)

Evidence for: Low‐grade inflammation mediated by gut microbial dysbiosis

Zheng et al. (2019) [42]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

Chinese population:

63 SZ, 69 HCs

Female: 33%, 48%

Age (years): 43.49 ± 1.68, 39.99 ± 1.62

BMI (kg/m²): 22.90 ± 0.32, 23.16 ± 0.33

Illness duration (N/A)

Antipsychotics (58 SZ)

N/A

Microbial α‐diversity ↓

Veillonellaceae and PANSS scores (−)

Lachnospiraceae and PANSS scores (+)

Microbial panel (Aerococcaceae,

Bifidobacteriaceae, Brucellaceae,

Pasteurellaceae, and Rikenellaceae)

for discriminating

SZ from HCs (ROC = 0.769)

Zhang et al. (2020) [43]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

Chinese population:

10 FSZ, 16 HCs

Female: 40%, 44%

Age (years): 37.6 ± 7.2, 35.8 ± 6.8

BMI (kg/m²): 23.3 ± 6.8, 22.3 ± 6.5

N/A

Microbial α‐diversity ↓

Phylum: Proteobacteria ↑

Genus: Faecalibacterium and

Lachnospiraceae ↓

Li et al. (2020) [44]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

Chinese population:

82 SZ, 80 HCs

Female: 44%, 51%

Age (years): 42.15 ± 13.13, 41.03 ± 14.34

BMI (kg/m²): 24.48 ± 4.33, 23.03 ± 3.05

Illness duration (N/A)

Antipsychotics (75 SZ)

N/A

Microbial α‐diversity (ns)

Phylum: Actinobacteria ↑; Firmicutes ↓

Genus: Collinsella, Lactobacillus,

Succinivibrio, Mogibacterium,

Corynebacterium ↑;

Adlercreutzia, Anaerostipes,

Ruminococcus and Faecalibacterium ↓.

Succinivibrio and PANSS scores (+)

Corynebacterium and PANSS scores (−)

Xu et al. (2020) [45]

Cross‐sectional study

Fecal samples

Shotgun sequencing

16S rRNA sequencing

Chinese population:

Discovery: 40 SZ, 40 HCs

Female: 50%, 50%. BMI: N/A

Age (years): 35 ± 11, 34 ± 9

Validation: 44 SZ, 44 HCs

Female: 36%, 36%

Age (years): 35 ± 11, 35 ± 11

BMI (kg/m²): 22.0 ± 3.2, 23.1 ± 3.7

Illness duration (N/A)

Antipsychotics (N/A)

N/A

Microbial α‐diversity ↓

Phylum: Actinobacteria ↑

Genus: Eggerthella and Megasphaera ↑;

Enterococcus ↓

Species: Akkermansia muciniphila,

Bifidobacterium adolescentis,

Clostridium perfringens,

Lactobacillus gasseri and

Megasphaera elsdeniis↑

Shen et al. (2018) [46]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

Chinese population:

64 SZ, 53 HCs

Female: 44%, 34%

Age (years): 42 ± 11, 39 ± 14

BMI (kg/m²): 23.49 ± 3.8, 23.14 ± 2.8

Illness duration ≤ 10 years

Antipsychotics >6 months

N/A

Microbial α‐diversity (ns)

Phylum: Proteobacteria ↑

Genus: Succinivibrio, Megasphaera,

Collinsella, Clostridium, Klebsiella,

Methanobrevibacter ↑;

Blautia, Coprococcus, Roseburia ↓.

Microbial panel discriminating

SZ from HCs (ROC = 0.837)

Schwarz et al. (2018) [48]

Cross‐sectional and

12 month follow‐up

Fecal samples

Shotgun sequencing

Finnish population:

28 FEP, 16 HCs

Female: 43%, 50%

Age (years): 25.9 ± 5.5, 27.8 ± 6.0

BMI (kg/m²): 23.8 ± 4.3, 23.9 ± 3.1

N/A

Genus: Lactobacillus, Tropheryma,

Halothiobacillus, Saccharophagus,

Ochrobactrum, Deferribacter and

Halorubrum ↑;

Anabaena, Nitrosospira, Gallionella,

Bacteroides, Ruminococcus,

and Faecalibacterium ↓

Lactobacillus and psychotic symptoms (+)

Lactobacillus and treatment response (−)

(up to 12 months)

Zhang et al. (2018) [49]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

Chinese population:

12 aSZ, 13 rSZ

Female: 50%, 46%

Age (years): 36.5 ± 8.9, 36.2 ± 8.2

BMI (kg/m²): 23.7 ± 3.2, 24.2 ± 2.7

Duration (years): 8.0 ± 6.9, 9.3 ± 6.4

Antipsychotics >6 months

N/A

aSZ (vs. rSZ):

Microbial α‐diversity ↓

Genus: Bacteroides ↑, Prevotella ↓

Genus Prevotella and PANSS scores (−)

Evidence against: Low‐grade inflammation mediated by gut microbial dysbiosis

Nguyen et al. (2018) [41]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

American population:

25 SZ, 25 HCs

Female: 40%, 44%

Age (years): 52.9 ± 11.2, 54.7 ± 10.7

BMI (kg/m²): 31.8 ± 5.4, 28.9 ± 4.0

Illness duration >10 years

Antipsychotics (21 SZ)

N/A

Microbial α‐diversity (ns)

Phylum: Proteobacteria ↓

Genus: Anaerococcus ↑;

Haemophilus, Sutterella, Clostridium ↓.

Family Ruminococcaceae and

Negative symptoms (−)

Ma et al. (2020) [50]

Cross‐sectional study

Fecal samples

16S rRNA sequencing

Chinese population:

(40 FSZ, 85 TSZ), 69 HCs

Female: 46%, 46%

Age (years): 24.19 ± 6.18, 23.14 ± 3.20

BMI: 18–25 kg/m²

Antipsychotics (TSZ) > 3 months

Illness duration (TSZ) > 1 year

N/A

FSZ (vs. HCs):

Microbial α‐diversity (ns)

Genus: Actinobacillus, Fusobacterium,

Megasphaera, SMB53 ↓; Escherichia ↑

TSZ (vs. FSZ and HCs):

Microbial α‐diversity ↓

Genus: Escherichia, Enterococcus,

Lactobacillus, Shigella, Streptococcus ↑

Abbreviations: aSZ, acute schizophrenia; BMI, body mass index; FEP, first‐episode psychosis; FSZ, first‐episode drug‐naïve schizophrenia; HCs, healthy controls; PANSS, positive and negative syndrome scale; ROC, receiver operating characteristic; rRNA, ribosomal RNA; rSZ, remission schizophrenia; SZ, schizophrenia; TSZ, chronically antipsychotic‐treated schizophrenia.