Gut microbial biomarkers for the treatment response in first-episode, drug-naïve schizophrenia: a 24-week follow-up study

Study information

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

34376634

DOI Digital object identifier for electronic documents.

10.1038/s41398-021-01531-3

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

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Curated date: 2024/07/29

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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: Schizophrenia [X]Schizophrenia, unspecified,[X]Schizophrenia, unspecified (disorder),Dementia Praecox,Disorder, Schizophrenic,Disorders, Schizophrenic,Other specified types of schizophrenia,Other specified types of schizophrenia, chronic state,Other specified types of schizophrenia, chronic state with acute exacerbation,Other specified types of schizophrenia, in remission,Other specified types of schizophrenia, subchronic state,Other specified types of schizophrenia, subchronic state with acute exacerbation,Other specified types of schizophrenia, unspecified state,SCHIZO NEC-CHR/EXACERB,SCHIZO NEC-SUBCHR/EXACER,SCHIZO NOS-CHR/EXACERB,SCHIZO NOS-SUBCHR/EXACER,schizoaffective disorder,schizophrenia,schizophrenia (disease),Schizophrenia (disorder),SCHIZOPHRENIA NEC-CHR,SCHIZOPHRENIA NEC-REMISS,SCHIZOPHRENIA NEC-SUBCHR,SCHIZOPHRENIA NEC-UNSPEC,Schizophrenia NOS,Schizophrenia NOS (disorder),SCHIZOPHRENIA NOS-UNSPEC,schizophrenia with or without an affective disorder,Schizophrenia, NOS,schizophrenia-1,Schizophrenias,SCHIZOPHRENIC DIS,Schizophrenic Disorder,Schizophrenic Disorders,Schizophrenic disorders (disorder),SCZD,Unspecified schizophrenia,Unspecified schizophrenia (disorder),Unspecified schizophrenia, chronic state with acute exacerbation,Unspecified schizophrenia, subchronic state with acute exacerbation,Unspecified schizophrenia, unspecified state,Schizophrenia

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: SCH patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: first-episode, drug-naïve SCH patients

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

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: Random Forest Analysis

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

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3.0

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

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Curated date: 2024/07/29

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Source: Figure 4

Description: "Dynamic changes of gut microbiota in SCH patients."

Abundance in Group 1: decreased abundance in SCH patients

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Romboutsia

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Signature 2

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Curated date: 2024/08/03

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Source: Figure 4

Description: "Dynamic changes of gut microbiota in SCH patients."

Abundance in Group 1: increased abundance in SCH patients

NCBI	Quality Control	Links
Lachnoclostridium

Revision editor(s): JoyceQ

Experiment 2

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incomplete

Curated date: 2024/07/29

Curator: JoyceQ

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Not specified

Group 1 name Corresponds to the case (exposed) group for case-control studies: Not specified

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Not specified

Group 0 sample size Number of subjects in the control (unexposed) group: Not specified

Group 1 sample size Number of subjects in the case (exposed) group: Not specified

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Not specified

Sequencing type: Not specified

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Not specified

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified

Statistical test: Not specified

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): Not specified

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Not specified

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: Not specified