Gut microbial biomarkers for the treatment response in first-episode, drug-naïve schizophrenia: a 24-week follow-up study
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yuan X, Wang Y, Li X, Jiang J, Kang Y, Pang L, Zhang P, Li A, Lv L, Andreassen OA, Fan X, Hu S, Song X
Journal
Translational psychiatry
Year
2021
Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson's indices) compared to HCs at baseline (p = 1.21 × 10-9, 1.23 × 10-8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.
Experiment 1
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to risperidone Response to risperidone,response to risperidone
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls (C)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Schizophrenia (SCH) patients at Baseline (S0)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Schizophrenia drug-naïve patients who were newly admitted, and no treatment had begun. Patients had not yet received risperidone.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 107
- Group 1 sample size Number of subjects in the case (exposed) group
- 107
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 30 days
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Ion Torrent
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, smoking behavior, education level, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, smoking behavior, education level, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Source: Figure 4c and Supplementary Table 3
Description: Taxa enriched in the gut microbiota of Schizophrenia (SCH) patients at Baseline (S0) and Healthy controls (C).
Abundance in Group 1: increased abundance in Schizophrenia (SCH) patients at Baseline (S0)
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnoclostridium |
Signature 2
Source: Figure 4d and Supplementary Table 3
Description: Taxa enriched in the gut microbiota of Schizophrenia (SCH) patients at Baseline (S0) and Healthy controls (C).
Abundance in Group 1: decreased abundance in Schizophrenia (SCH) patients at Baseline (S0)
Experiment 2
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Schizophrenia (SCH) patients at Week 6 (S1)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Schizophrenia drug-naïve patients who had received 6 weeks of risperidone treatment and were accessed during the treatment.
- Group 1 sample size Number of subjects in the case (exposed) group
- 96
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 4C
Description: Taxa enriched in the gut microbiota of Schizophrenia (SCH) patients at Week 6 (S1) and Healthy controls (C).
Abundance in Group 1: decreased abundance in Schizophrenia (SCH) patients at Week 6 (S1)
| NCBI | Quality Control | Links |
|---|---|---|
| Romboutsia |
Revision editor(s): MyleeeA
Experiment 3
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Schizophrenia (SCH) patients at Week 12 (S2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Schizophrenia drug-naïve patients who had received 12 weeks of risperidone treatment and were accessed during the treatment.
- Group 1 sample size Number of subjects in the case (exposed) group
- 74
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 30 Days
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 4C
Description: Taxa enriched in the gut microbiota of SCH patients at Week 12 (S2) and Healthy controls (C).
Abundance in Group 1: decreased abundance in Schizophrenia (SCH) patients at Week 12 (S2)
| NCBI | Quality Control | Links |
|---|---|---|
| Romboutsia |
Revision editor(s): MyleeeA
Experiment 4
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Schizophrenia (SCH) patients at Week 24 (S3)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Schizophrenia drug-naïve patients who had received 24 weeks of risperidone treatment and were accessed after the treatment.
- Group 1 sample size Number of subjects in the case (exposed) group
- 60
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 30 days
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, education level, sex, smoking behavior
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, education level, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Needs review
Source: Figure 4d
Description: Taxa enriched in the gut microbiota of SCH patients at Week 24 (S3) and Healthy controls (C).
Abundance in Group 1: decreased abundance in Schizophrenia (SCH) patients at Week 24 (S3)
| NCBI | Quality Control | Links |
|---|---|---|
| Romboutsia |
Revision editor(s): Aleru Divine
Experiment 5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Schizophrenia (SCH) patients at Baseline (S0)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Schizophrenia (SCH) patients at Week 12 (S2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Schizophrenia drug-naïve patients who had received 12 weeks of risperidone treatment and were accessed during the treatment.
- Group 1 sample size Number of subjects in the case (exposed) group
- 74
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Experiment 6
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Schizophrenia (SCH) patients at Week 24 (S3)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Schizophrenia drug-naïve patients who had received 24 weeks of risperidone treatment and were accessed after the treatment.
- Group 1 sample size Number of subjects in the case (exposed) group
- 60
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 30 Days
Lab analysis
Statistical Analysis
- Statistical test
- LEfSe
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 3
Signature 1
Source: Supplementary Figure S5
Description: Taxa enriched in the gut microbiota of Schizophrenia (SCH) patients at Baseline(S0) and After treatment at Week 24 (S3)
Abundance in Group 1: increased abundance in Schizophrenia (SCH) patients at Week 24 (S3)
Revision editor(s): MyleeeA
Signature 2
Needs review
Source: Supplementary Figure 5 and Figure 4c
Description: Taxa enriched in the gut microbiota of Schizophrenia patients at Baseline(S0) and After treatment at Week 24 (S3)
Abundance in Group 1: decreased abundance in Schizophrenia (SCH) patients at Week 24 (S3)
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnoclostridium |
Revision editor(s): Aleru Divine, MyleeeA
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