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

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Reviewed Marked as Reviewed by Svetlana up on 2024-12-16
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


Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/07/29

Curator: JoyceQ

Revision editor(s): JoyceQ, MyleeeA, KateRasheed

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, Confounders controlled for: "disease duration" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.disease duration

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

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/07/29

Curator: JoyceQ

Revision editor(s): JoyceQ, MyleeeA

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 ControlLinks
Lachnoclostridium

Revision editor(s): JoyceQ, MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/08/03

Curator: JoyceQ

Revision editor(s): JoyceQ, MyleeeA

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)

NCBI Quality ControlLinks
unclassified Eubacteriales
Alistipes
Blautia
unclassified Lachnospiraceae
Bifidobacterium
Romboutsia
Fusobacterium
Anaerostipes
Dorea
Streptococcus
Fusicatenibacter
unclassified Erysipelotrichaceae
Lactococcus
Weissella
Terrisporobacter
Haemophilus
Enterococcus
Citrobacter

Revision editor(s): JoyceQ, MyleeeA

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/07/29

Curator: JoyceQ

Revision editor(s): JoyceQ, MyleeeA, KateRasheed

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

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/14

Curator: MyleeeA

Revision editor(s): MyleeeA

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 ControlLinks
Romboutsia

Revision editor(s): MyleeeA

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/14

Curator: MyleeeA

Revision editor(s): MyleeeA, KateRasheed

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

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/14

Curator: MyleeeA

Revision editor(s): MyleeeA

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 ControlLinks
Romboutsia

Revision editor(s): MyleeeA

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/14

Curator: MyleeeA

Revision editor(s): MyleeeA, KateRasheed

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, education level, sex, smoking behavior, Confounders controlled for: "disease duration" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.disease duration

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

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/18

Curator: Aleru Divine

Revision editor(s): Aleru Divine

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 ControlLinks
Romboutsia

Revision editor(s): Aleru Divine

Experiment 6


Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/14

Curator: MyleeeA

Revision editor(s): MyleeeA, KateRasheed

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)
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

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/16

Curator: MyleeeA

Revision editor(s): MyleeeA

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)

NCBI Quality ControlLinks
Gammaproteobacteria
unidentified Gammaproteobacteriaunidentified Gammaproteobacteria
Lachnospira
Sutterella
Rickenellaceae
Alistipes
Burkholderiaceae
Acetitomaculum
Clostridium sp. MC 40
Oscillibacter sp. ER4
Firmicutes bacterium CAG_194_44_15
Lactobacillales
Bacilli

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-16

Curated date: 2024/10/18

Curator: Aleru Divine

Revision editor(s): Aleru Divine, MyleeeA

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 ControlLinks
Lachnoclostridium

Revision editor(s): Aleru Divine, MyleeeA