The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice

Study information

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study design

case-control

Citation

PMID PubMed identifier for scientific articles.

30775438

DOI Digital object identifier for electronic documents.

10.1126/sciadv.aau8317

URI

Authors

Zheng P, Zeng B, Liu M, Chen J, Pan J, Han Y, Liu Y, Cheng K, Zhou C, Wang H, Zhou X, Gui S, Perry SW, Wong ML, Licinio J, Wei H, Xie P

Journal

Science advances

Year

2019

Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-25

Curated date: 2024/07/23

Curator: Jacob A. De Jesus

Revision editor(s): Jacob A. De Jesus

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: HC: individuals without a psychiatric diagnosis of schizophrenia

Group 1 name Corresponds to the case (exposed) group for case-control studies: SCZ: individuals with a psychiatric diagnosis of schizophrenia

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: individuals with schizophrenia diagnosed by Structured Psychiatric Interview using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)

Group 0 sample size Number of subjects in the control (unexposed) group: 69

Group 1 sample size Number of subjects in the case (exposed) group: 63

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

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: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Alpha Diversity

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Richness Number of species: decreased

Signature 1

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Curated date: 2024/07/23

Curator: Jacob A. De Jesus

Revision editor(s): Jacob A. De Jesus

Source: Table S2A

Description: Up-regulated relative abundance of operational taxonomic units in individuals with schizophrenia compared to normal controls.

Abundance in Group 1: increased abundance in SCZ: individuals with a psychiatric diagnosis of schizophrenia

NCBI	Quality Control	Links
uncultured Acidaminococcus sp.
Sutterella wadsworthensis 2_1_59BFAA
Alloscardovia omnicolens
Bacteroides cellulosilyticus DSM 14838
Bacteroides thetaiotaomicron
unclassified Bacteroides
uncultured Sarcina sp.
unclassified Atopobium
metagenome
Flavobacterium anhuiense
unclassified Fusobacterium
uncultured Alloprevotella sp.
uncultured Prevotella sp.
human gut metagenome
Flavonifractor plautii
uncultured Dialister sp.
Megasphaera elsdenii DSM 20460
unclassified Megasphaera
unclassified Veillonella
unclassified Akkermansia

Revision editor(s): Jacob A. De Jesus

Signature 2

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Curated date: 2024/07/24

Curator: Jacob A. De Jesus

Revision editor(s): Jacob A. De Jesus

Source: Table S2A

Description: Down-regulated relative abundance of operational taxonomic units in individuals with schizophrenia compared to normal controls.

Abundance in Group 1: decreased abundance in SCZ: individuals with a psychiatric diagnosis of schizophrenia

NCBI	Quality Control	Links
Alistipes putredinis DSM 17216
Bacteroides
Bacteroides eggerthii
Candidatus Saccharibacteria bacterium UB2523
Collinsella stercoris
Eubacterium coprostanoligenes
Eubacterium ventriosum
Gemella sanguinis
Haemophilus parainfluenzae T3T1
Lachnospiraceae bacterium NK4A136
Odoribacter splanchnicus DSM 20712
Phascolarctobacterium
Phocaeicola massiliensis
Raoultella ornithinolytica B6
Ruminococcaceae bacterium UCG-005
Ruminococcus bicirculans (ex Liu et al. 2021)
Streptococcus salivarius
TM7 phylum sp. oral clone DR034
TM7 phylum sp. oral clone FR058
[Ruminococcus] torques ATCC 27756
unclassified Bacteroides
unclassified Barnesiella
unclassified Blautia
unclassified Candidatus Saccharibacteria
unclassified Coprococcus
unclassified Dialister
unclassified Fusicatenibacter
unclassified Klebsiella
unclassified Lachnospiraceae
unclassified Methylobacterium
unclassified Streptococcus
uncultured Citrobacter sp.
uncultured Dorea sp.
uncultured Erysipelotrichaceae bacterium
uncultured Granulicatella sp.
uncultured Hafnia sp.
uncultured Lachnoclostridium sp.
uncultured Lachnospiraceae bacterium
uncultured Mollicutes bacterium
uncultured Oscillospiraceae bacterium
uncultured Ruminiclostridium sp.
uncultured Ruminococcus RM2
uncultured Ruminococcus sp.

Revision editor(s): Jacob A. De Jesus