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. 2021 Mar 31;13(4):1152. doi: 10.3390/nu13041152

Table 1.

Summary of studies investigating the microbiome in patients with schizophrenia.

Publication Study Design Diversity Findings Taxa Abundance Differences in Schizophrenia
He et al., 2018 [33] Gut microbiome

81 high-risk schizophrenia patients, 19 ultra-high-risk schizophrenia patients, 69 healthy controls

Recruited from the Second Xiangya Hospital, Central South University, Changsha, Hunan, China

Experimental Method: 16S rRNA gene sequencing from stool samples collected at baseline
No significant differences between the groups Observed increased relative abundance of various taxa in schizophrenia:
Orders: Bacteroidales, Clostridiales, Lactobacillales
Genera: Lactobacillus, Prevotella
Species: Lactobacillus ruminis
Castro-Nallar et al., 2015 [34] Oral microbiome

16 schizophrenia patients, 16 healthy controls

Recruited from the Stanley Research Program at Sheppard Pratt Hospital Maryland, US

Experimental Method: Illumina sequencing of DNA from throat swabs
Lower species richness and more homogenously distributed in schizophrenia patients Observed increased relative abundance of various taxa in schizophrenia:
Phyla: Firmicutes
Genera: Bifidobacterium, Lactobacillus
Species: Bifidobacterium pseudocatenulatum, Candida dubliniensis, Catenibacterium mitsuokai, Eubacterium hallii, Lactobacillus gasseri, Lactobacillus salivarius
Yolken et al., 2020 [35] Oral microbiome

121 schizophrenia patients, 85 healthy controls

Recruited from psychiatric programs affiliated with the Sheppard Pratt Health System and at other outpatient treatment sites in central Maryland, US

Experimental Method: 16S rRNA gene sequencing of V3–V4 region from throat swabs
No significant differences in alpha diversity (microbial richness and diversity) were found

Altered beta diversity was found in individuals with schizophrenia compared to healthy controls
Observed increased relative abundance of various taxa in schizophrenia:
Genera: Streptococcus

Observed decreased relative abundance of various taxa in schizophrenia:
Families: Weeksellaceae
Genera: Prevotella
Species: Neisseria subflava
Zhang et al., 2020 [36] Gut microbiome

10 antipsychotic-naïve patients with first-episode schizophrenia, 16 healthy controls

Recruited from the Seventh People’s Hospital of Hangzhou in Hangzhou, Zhejiang

Experimental Method: 16S rRNA gene sequencing from stool samples collected at baseline
No significant differences in alpha diversity (microbial richness and diversity) were found

Principle coordinate analysis distinguished a cluster between the two groups, indicating a significant decrease in beta diversity in the schizophrenia group compared to the control group
Observed increased relative abundance of various taxa in schizophrenia:
Phyla: Proteobacteria
Classes: Deltaproteobacteria, Saccharimonadia, Synergistia
Orders: Actinomycetales, Desulfovibrionales, Saccharimonadales, Synergistales
Families: Actinomycetaceae, Burkholderiaceae, Desulfovibrionaceae, Saccharimonadaceae, Synergistaceae
Genera: Actinomyces, Anaerotruncus, Bilophila, Blautia, Christensenella, Cloacibacillus, Dorea, Eggerthella, Eisenbergiella, Flavonifractor, Holdemania, Hungatella, Oscillibacter, Parasutterella, Prevotella

Observed decreased relative abundance of various taxa in schizophrenia:
Families: Lachnospiraceae
Genera: Agathobacter, Butyricicoccus, Coprococcus, Faecalibacterium, Fusicatenibacter, Ruminococcus
Yuan et al., 2018 [37] Gut microbiome

41 antipsychotic naïve patients with first-episode schizophrenia and 41 healthy controls

Patients were started on risperidone treatment for 24 weeks (1–6 mg/day)

Recruited from First Affiliated Hospital of Zhengzhou University

Experimental Method: 16S rRNA gene sequencing from stool samples collected from baseline, weeks 6, 12 and 24
Not reported Abundance of Bifidobacterium spp. and Escherichia coli increased with risperidone treatment
Abundance of Lactobaccillus spp. and Clostridium coccoides decreased with risperidone treatment

Observed increased relative abundance of various taxa in schizophrenia:
Species: Clostridium coccoides

Observed decreased relative abundance of various taxa in schizophrenia:
Genera: Bifidobacterium., Lactobacillus
Species: Escherichia coli
Zhu et al., 2020 [38] Gut microbiome

90 antipsychotic-free patients with first-episode schizophrenia and 81 healthy controls

Followed up with 38 patients after 3 months of treatment (27 risperidone and 11 other antipsychotics)

Recruited from multiple clinical sites across the Shaanxi Province, China

Experimental Method: Metagenomic shotgun sequencing from stool samples collected at baseline and 3 months after antipsychotic treatment
Higher alpha diversity (microbial richness and diversity) was observed at the genus level

Individuals with schizophrenia presented with a more variable gut microbiome compared to healthy controls
Observed increased relative abundance of various
Species in chronically antipsychotic-treated schizophrenia compared to:
HC: Acidaminococcus fermentans, Acidaminococcus intestini, Akkermansia muciniphila, Alkaliphilus oremlandii, Bacillus amyloliquefaciens, Bacteroides plebeius, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium dentium, Bifidobacterium longum, Enterococcus faecium, Eubacterium siraeum, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus oris, Lactobacillus ruminis, Lactobacillus salivarius, Methanobrevibacter smithii, Pseudoflavonifractor capillosus, Stenotrophomonas maltophilia, Streptococcus anginosus, Streptococcus mutans, Veillonella atypica, Veillonella parvula
FSCZ: Actinomyces odontolyticus, Enterobacter aerogenes, Enterobacter asburiae, Enterobacter cancerogenus, Enterobacter cloacae, Escherichia coli, Lactococcus lactis, Victivallis vadensis,

Observed decreased relative abundance of various
Species in chronically antipsychotic-treated schizophrenia compared to:
HC: Bacteroides intestinalis, Lactobacillus acidophilus, Lactococcus lactis
FSCZ: Alkaliphilus oremlandii, Anaerostipes caccae, Bacteroides ovatus, Bifidobacterium angulatum, Bifidobacterium bifidum, Bifidobacterium longum, Clostridium bolteae, Dorea formicigenerans, Enterococcus faecium, Eubacterium hallii, Faecalibacterium prausnitzii, Lactobacillus ruminis, Streptococcus anginosus

Observed increased relative abundance of various
Genera in first-episode schizophrenia compared to controls: Acidaminococcus, Akkermansia, Anaerotruncus, Bifidobacterium, Citrobacter, Clavibacter, Comamonas, Coprobacillus, Cryptobacterium, Dialister, Enterococcus, Lactobacillus, Methanobrevibacter, Peptoniphilus, Pseudoflavonifractor, Veillonella

Observed decreased relative abundance of various
Genera in first-episode schizophrenia compared to controls: Butyrivibrio, Gemella
Pełka-Wysiecka et al., 2019 [39] Gut microbiome

20 schizophrenia patients

Patients underwent a 7 day washout and were started on olanzapine for 2 weeks (5–20 mg/day).

Recruited from Department of Psychiatry in Szczecin (Poland)

Experimental Method: 16S rRNA gene sequencing of V4 region from stool samples collected after washout and week 2 of treatment.
No significant changes in alpha diversity after 2 weeks of olanzapine treatment No significant changes in OTU abundancies between weeks 0 and 6.

No changes in Firmicutes/Bacteroidetes ratio
Shen et al., 2018 [40] Gut microbiome

64 schizophrenia patients on antipsychotic medication and 53 healthy controls

Recruited from hospital or outpatient clinics within Huludao area in China

Experimental Method: 16S rRNA gene sequencing of V3–V4 region from stool samples collected at baseline
No significant differences in alpha diversity (microbial richness and diversity) were found
Observed increased relative abundance of various taxa in schizophrenia:
Phyla: Proteobacteria
Classes: Gammaproteobacteria
Orders: Aeromonadales, Fusobacteriales
Families: Enterobacteriaceae, Fusobacteriaceae, Lactobacillaceae, Prevotellaceae, Succinivibrionaceae, Veillonellaceae
Genera: Acidaminococcus, Citrobacter, Clostridium, Collinsella, Desulfovibrio, Fusobacterium, Klebsiella, Lactobacillus, Megasphaera, Phascolarctobacterium, Prevotella, Succinivibrio
Species: Bifidobacterium adolescentis, Bacteroides fragilis, Collinsella aerofaciens, Lactobacillus mucosae, Prevotella stercorea

Observed decreased relative abundance of various taxa in schizophrenia:
Phyla: Firmicutes
Classes: Clostridia
Orders: Clostridiales
Families: Alkaligenaceae, Lachnospiraceae
Genera: Blautia, Coprococcus, Roseburia, Streptococcus
Species: Bacteroides eggerthii, Blautia producta, Collinsella plebeius, Roseburia faecis
Nguyen et al., 2019 [41] Gut microbiome

25 patients with chronic schizophrenia or schizoaffective disorder (most patients were being treated with antipsychotic medication), 25 demographically matched non-psychiatric controls

Recruited as outpatients in San Diego

Experimental Method: 16S rRNA gene sequencing of V4 region from stool samples collected at baseline
No significant differences in alpha diversity (microbial richness and diversity) were found Observed increased relative abundance of various taxa in schizophrenia:
Genera: Anaerococcus, Blautia, Megasphaera,, Ruminococcus

Observed decreased relative abundance of various taxa in schizophrenia:
Phyla: Proteobacteria
Genera: Clostridium, Haemophilus, Oscillospira, Sutterella
Species: Haemophilus parainfluenzae
Zheng et al., 2019 [42] Gut microbiome

63 schizophrenia patients (most patients were being treated with antipsychotic medication), 69 healthy controls

Recruited from the First Affiliated Hospital of Chongqing Medical University

Experimental Method: 16S rRNA gene sequencing of V3–V4 region from stool samples collected at baseline
Lower alpha diversity (species richness and diversity) was observed in schizophrenia patients Observed increased relative abundance of various taxa in schizophrenia:
Families: Bacteroidaceae, Coriobacteriaceae, Prevotellaceae, Veillonellaceae
Genera: Akkermansia, Fusobacterium, Megasphaera, Prevotella

Observed decreased relative abundance of various taxa in schizophrenia:
Families: Acidaminococcaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, Ruminococcaceae
Genera: Blautia, Citrobacter, Coprococcus, Lachnoclostridium
Species: Bacteroides eggerthii, Bacteroides massiliensis, Collinsella stercoris, Haemophilus parainfluenzae
Ma et al., 2020 [43] Gut microbiome

40 antipsychotic-naïve patients with first-episode schizophrenia (FSCZ), 85 chronically antipsychotic-treated schizophrenia patients, 69 healthy controls (HC)

Recruited from the Second Xiangya Hospital of Central South University

Experimental Method: 16S rRNA gene sequencing of V4 region from stool samples collected at baseline
Lower alpha diversity (species richness and diversity) was observed in chronically antipsychotic-treated schizophrenia patients compared to antipsychotic-naïve patients with first-episode schizophrenia and healthy controls Observed increased relative abundance of various taxa in chronically antipsychotic-treated schizophrenia compared to:
Phyla
HC: Proteobacteria
Families
HC: Christensenellaceae, Enterobacteriaceae, Enterococcaceae, Lactobacillaceae
FSCZ: Enterococcaceae, Lactobacillaceae, Peptostreptococcaceae. Streptococcaceae, Veillonellaceae
Genera
HC: Escherichia, Bulleidia, Coprobacillus, Enterococcus, Lactobacillus, Shigella, Streptococcus, Trabulsiella, Veillonella
FSCZ: Citrobacter, Clostridium, Enterobacter, Enterococcus, Escherichia, Fusobacterium, Lachnobacterium, Megasphaera, Lactobacillus, Ruminococcus, Shigella, Streptococcus, Sutterella, Veillonella

Observed decreased relative abundance of various taxa in chronically antipsychotic-treated schizophrenia compared to:
Phyla
HC: Cyanobacteria
FSCZ: Lentisphaerae
Families
HC: Pasteurellaceae, Turicibacteraceae
Genera
HC: Bacteroides, Parabacteroides, Turicibacter
FSCZ: Lachnobacterium
Xu et al., 2020 [44] Gut microbiome

44 schizophrenia patients, 44 healthy controls

Recruited from Longgang Central Hospital of Shenzhen and Shenzhen Kangning Hospital in Shenzhen, China

Experimental Method: 16S rRNA gene sequencing of V4 region from stool samples collected at baseline
Lower species richness was observed in schizophrenia patients

NMDS analysis at the species level resulted in distinct clusters with few overlaps between schizophrenia patients and healthy controls.

The microbial dysbiosis index was significantly increased in patients with schizophrenia compared to controls.
Observed increased relative abundance of various taxa in schizophrenia:
Phyla: Actinobacteria
Classes: Deltaproteobacteria
Orders: Actinomycetales, Sphingomonadales
Families: Sphingomonadaceae
Genera: Eggerthella, Megasphaera
Species: Akkermansia muciniphila, Bifidobacterium adolescentis, Clostridium perfringens, Lactobacillus gasseri, Megasphaera elsdeniis

Observed decreased relative abundance of various taxa in schizophrenia:
Orders: Rhodocyclales
Families: Alcaligenaceae, Enterococcaceae, Leuconostocaceae, Rhodocyclaceae, Rikenellaceae
Genera: Enterococcus

Experimental Methods and Taxonomic Groups are in bold.