Table 2.
Gut microbiota changes in schizophrenic patients and at risk individuals.
| Patient Characteristics(N, Gender, Age) | Exclusion/Inclusion criteria | Microbiota analysis | Microbiota findings at Baseline compared to control | Other findings | Comments | |
|---|---|---|---|---|---|---|
| He, Kosciolek (4) | • HR (41M, 40F, 21.67 ± 5.75) • UHR (15M, 4F, 20.47 ± 4.57) • HC (37M, 32F, 23.13 ± 3.89) |
Exclusion: • Gastrointestinal and endocrine diseases • Diagnosis with psychotic disorder and corresponding treatments • Last 3 month: alcohol, antibiotics, probiotics or any other oral or injectable medications |
• One measure at baseline | No difference • α-diversity Altered: • β-diversity in HR and UHR Increased in UHR: • Clostridiales (Phylum: Firmicutes) • Lactobacillales (Phylum: Firmicutes) • Bacteroidales (Phylum: Bacteroidetes) • Lactobacillus (Phylum: Firmicutes) • Prevotella (Phylum: Bacteroidetes) • Lactobacillus ruminis (Phylum: Firmicutes) No Change • HR group |
No difference: • Age and gender Increased: • Symptoms in UHR • Choline levels in UHR |
• HC: no family history of mental illness • 37 HC did not agree with 1H-MRS • 1H-MRS: 7 HR and 2 UHR excluded |
| Schwarz, Maukonen (54) | • FEP (16M, 12, 25.9 ± 5.5) • HC (8M, 8F, 27.8 ± 6.0) |
Exclusion: • Substance-induced psychosis and psychotic disorders due to general medical conditions Inclusion: • Score of at least 4 in the item assessing delusion (Usual Thought Content) and hallucinations (Brief Psychiatric rating scale) |
• FEP: Morning of interview • HC: Sample at home and delivered them within a few hours to the laboratory • Baseline, 2 and 12 month |
No difference • α-diversity Increased: • Phylum Actinobacteria • Rhizobiales (Phylum: Proteobacteria) • Bacillales (Phylum: Firmicutes) • Lactobacillaceae (Phylum: Firmicutes) • Halothiobacillaceae (Phylum: Proteobacteria) • Brucellaceae (Phylum: Proteobacteria) • unclassified Micrococcineae (Phylum: Actinobacteria) • Lactobacillus (Phylum: Firmicutes) • Tropheryma (Phylum: Actinobacteria) • Halothiobacillus (Phylum: Proteobacteria) • Saccharophagus (Phylum: Proteobacteria) • Ochrobactrum` (Phylum: Proteobacteria) • Deferribacter (Phylum: “Deferribacteres”) • Halorubrum (Phylum: Euryarchaeota) • Lactobacillus aciddophilus (Phylum: Firmicutes) • Lactobacillus grasser (Phylum: Firmicutes) • Lactobacillus saliva (Phylum: Firmicutes) • Lactobacillus reuter (Phylum: Firmicutes) • Lactobacillus fermen (Phylum: Firmicutes) • Desulfosporosinus acidphilus (Phylum: Firmicutes) • Bifidobacterium dentium (Phylum: Actinobacteria) • Tropheryma whipplei (Phylum: Actinobacteria) • Ochrobactum anthropi (Phylum: Proteobacteria) • Bartonella clarridgeiae (Phylum: Proteobacteria) • Franisella hispaniensis (Phylum: Proteobacteria) • Nitrosocococcus halophilus (Phylum: Proteobacteria) • Brucella canis (Phylum: Proteobacteria) • Saccharophagus degradans (Phylum: Proteobacteria) • Halothiobacillus neapolitanus (Phylum: Proteobacteria) • Deferribacter desulfuricans (Phylum: “Deferribacteres”) Decreased: • Negativicutes (Phylum: Firmicutes) • Selenomondales (Phylum: Firmicutes) • Veillonellaceae (Phylum: Firmicutes) • Anabaena (Phylum: Cyanobacteria) • Nitrosospira (Phylum: Proteobacteria) • Gallionella (Phylum: Proteobacteria) • Thermococcos gammatolerans (Phylum: Euryarchaeota) • Leuconostoc gasicomitatum (Phylum: Firmicutes) • Nitrosomonas spp. (Phylum: Proteobacteria) • Anabaena variabilities (Phylum: Cyanobacteria) • Gallionella capsiferriformans (Phylum: Proteobacteria) • Chlorobium chlorochromate (Phylum: Chlorobi) • Nitrosospira multiformis (Phylum: Proteobacteria) • Xenorhabdus nematophila (Phylum: Proteobacteria) In active SZ patients Increased: • Lactobacillaceae (Phylum: Firmicutes) Decreased: • Veillonellaceae (Phylum: Firmicutes *Correlations described in text |
No difference: • Age, gender and several metabolic parameters (BMI, cholesterol, high and low density lipoproteins, glucose, insulin and triglycerides) • SZ patient less active Cofounders-no association: • Physical activity • Type of psychosis • Duration of antipsychotic treatment • Distribution of risperidone, quetiapine or olanzapine treatment • Intake of different food types over the week prior to sample collection |
• Food habits and physical activity assessed • Fecal sample not collected if: antibiotic use during the past 3 months, chronic gastrointestinal disease, gastrointestinal surgery, or diagnosed celiac disease. • Microbiota clustering at intake was significantly associated with remission at follow-up |
| Shen, Xu (57) | • SZ (M36, F28, 42 ± 11) • HC (M35, F18, 39 ± 14) |
Exclusion: • Last 3 month: Disease that may affect the stability of gut microbiota • Last 6 months: antibiotics, glucocorticoids, cytokines, large doses of probiotics and biological agents • Gastroscopy, colonoscopy or gastrointestinal barium meal • Last 5 years: major gastrointestinal tract surgery • Activity limitation • Changes in dietary habits • Alcohol abuse or dependence Inclusion: • SZ patients were diagnosed according to ICD-10 and received antipsychotic treatment in hospital or outpatient clinic • Illness duration ≤10 years and received antipsychotic drugs treatment > 6months; psychiatric symptoms were steady >3 months, and the PANSS evaluated the rate of change ≤20% and the total score of PANSS ≤60. |
• One measure at baseline | No difference • α-diversity Altered: • β-diversity Increased: • Phylum Proteobacteria • Phylum Fusobacteria • Gammaproteobacteria (Phylum: Proteobacteria) • Fusobacteriia (Phylum: Fusobacteria) • Enterobacteriales (Phylum: Proteobacteria) • Fusobacteriales (Phylum: Fusobacteria) • Aeromonadales (Phylum: Proteobacteria) • Prevotellaceae (Phylum: Bacteroidetes) • Enterobacteriaceae (Phylum: Proteobacteria) • Succinivibrionaceae (Phylum: Proteobacteria) • Fusobacteriaceae (Phylum: Fusobacteria) • Veillonellaceae (Phylum: Firmicutes) • Lactobacillaceae (Phylum: Firmicutes) • Succinivibrio (Phylum: Proteobacteria) • Megasphaera (Phylum: Firmicutes) • Acidaminococcus (Phylum: Firmicutes) • Collinsella (Phylum: Actinobacteria) • Clostridium (Phylum: Firmicutes) • Klebsiella (Phylum: Proteobacteria) • Citrobacter (Phylum: Proteobacteria) • Methanobrevibacter (Phylum: Euryarchaeota) • Fusobacterium (Phylum: Fusobacteria) • Lactobacillus (Phylum: Firmicutes) • Phascolarctobacterium (Phylum: Firmicutes) • Desulfovibrio (Phylum: Firmicutes) • Collinsella aerofaciens (Phylum: Actinobacteria) • Bifidobacterium adolescentis (Phylum: Actinobacteria) • Prevotella stercorea (Phylum: Bacteroidetes) • Bacteroides fragilis (Phylum: Bacteroidetes) • Lactobacillus mucosae (Phylum: Firmicutes) • Lactobacillus ruminis (Phylum: Firmicutes) Decreased: • Phylum Firmicutes • Clostridia (Phylum: Firmicutes) • Clostridiales (Phylum: Firmicutes) • Streptococcaceae (Phylum: Firmicutes) • Alcaligenaceae (Phylum: Proteobacteria) • Lachnospiraceae (Phylum: Firmicutes) • Streptococcus (Phylum: Firmicutes) • Blautia (Phylum: Firmicutes) • Coprococcus (Phylum: Firmicutes) • Roseburia (Phylum: Firmicutes) • Roseburia faecis (Phylum: Firmicutes) • Blautia producta (Phylum: Firmicutes) • Collinsella plebeius (Phylum: Actinobacteria) • Bacteroides eggerthii (Phylum: Bacteroidetes) *Correlations described in text |
No difference: • Age, BMI, sex ratio, tobacco used and alcohol intake |
|
| Yuan, Zhang (55) | • FES (M23, F18, 23.1 ± 8.0) • HC (M20, F21, 24.7 ± 6.7) |
Exclusion • Autoimmune diseases, heart diseases, hepatobiliary and gastrointestinal diseases, blood diseases, diabetes neurological diseases, or psychiatric diseases other than FES • Pregnant or lactating women • A history of using any antibiotic or anti-inflammatory agent, or probiotic in the past month • A significant change in the living environment or diet in the past month • Significant diarrhea or constipation in the past month. Healthy controls had the same exclusion criteria as patients; in addition, they had no previous history of any psychiatric diseases. Inclusion • FES based on the DSM-IV criteria • Never been on antipsychotic medication • PANSS total score N60 points • Born through normal vaginal delivery • Normal body weight (BMI: 18.5–23.0). |
• Baseline, 6,12,24 weeks of risperidone treatment | Increased: • Clostridium coccoides group (Phylum: Firmicutes) Decreased: • Bifidobacterium spp. (Phylum: Actinobacteria) • Escherichia coli (Phylum: Proteobacteria) • Lactobacillus spp. (Phylum: Firmicutes) No Change: • Bacteroides spp. (Phylum: Bacteroidetes) After 24 weeks risperidone- Increased: • Bifidobacterium spp. (Phylum: Actinobacteria) • Escherichia coli (Phylum: Proteobacteria) Decreased: • Clostridium coccoides group (Phylum: Firmicutes) • Lactobacillus spp. (Phylum: Firmicutes) No Change: • Bacteroides spp. (Phylum: Bacteroidetes) *Correlations described in text |
After 24 weeks risperidone- Increased: • Weight • BMI • Fasting serum levels of glucose • Triglycerides • LDL • HOMA-IR • Serum levels of hs-CRP • SOD |
|
| Nguyen, Kosciolek (56) | • SZ or schizoaffective disorder (14M, 11F, 52.9 ± 11.2) • HC (15M, 10F, 54.7 ± 10.7) |
Exclusion • Other current major DSM-IV-TR Axis I diagnoses • Alcohol or other substance (other than tobacco) (within 3 months prior to enrollment) • Diagnosis of dementia • Intellectual disability disorder, • Major neurological disorder • Any medical disability that interfered with a subject’s ability to complete study procedures |
• One measure • Home stool collection kits (samples returned via mail) |
No difference • α-diversity Altered: • β-diversity Increased: • Anaerococcus (Phylum: Firmicutes) Decreased: • Phylum Proteobacteria • Haemophilus (Phylum: Proteobacteria) • Sutterella (Phylum: Proteobacteria) • Clostrodium (Phylum: Firmicutes) *Correlations described in text |
No difference: • Age, gender, race Increased: • BMI (however, no differences in BMI classifications) • Psychiatric symptoms • Depression levels • Anxiety levels • Smoking • Medical comorbidity (diabetes and hypertension) Decreased: • Physical well-being |
• 21 patients on antipsychotics at study onset |
| Zheng, Zeng (40) | • SZ (63) • HC (69) |
Exclusion • Physical or other mental disorders • Illicit drug use • Antibiotics/probiotics within 1 month of study |
• | Decreased: • α-diversity Altered: • β-diversity Increased: • Veillonellaceae (Phylum: Firmicutes) • Prevotellaceae (Phylum: Bacteroidetes) • Bacteroidaceae (Phylum: Bacteroidetes) • Coriobacteriaceae (Phylum: Actinobacteria) Decreased: • Lachnospiraceae (Phylum: Firmicutes) • Ruminococcaceae (Phylum: Firmicutes) • Enterobacteriaceae (Phylum: Proteobacteria) *Correlations described in text and comparison to depressive disorder and FMT from human to mouse |
No difference: • Age, gender, BMI Increased: • Serum glutamine • Hippocampal GABA Decreased: • Stool and hippocampal glutamate |
SZ were treated with a single antipsychotic drug: • Clozapine (n = 15) • Risperidone (n = 14) • Olanzapine (n = 9) • Chlorpromazine (n = 5) • Aripiprazole (n = 3) • Quetiapine (n = 3) • Remaining patients were treated with two of the above drugs in combination (n = 9) • Unmedicated (n = 5). |
SZ, schizophrenia; HR, high-risk; UHR, ultrahigh-risk, HC, healthy controls; FEP, first-episode psychosis; FES, first-episode schizophrenia; BMI, body mass index; PANSS, Positive and Negative Syndrome Scale.