Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice

Study information

Needs review

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

31391545

DOI Digital object identifier for electronic documents.

10.1038/s41380-019-0475-4

URI

Authors

Zhu F, Guo R, Wang W, Ju Y, Wang Q, Ma Q, Sun Q, Fan Y, Xie Y, Yang Z, Jie Z, Zhao B, Xiao L, Yang L, Zhang T, Liu B, Guo L, He X, Chen Y, Chen C, Gao C, Xu X, Yang H, Wang J, Dang Y, Madsen L, Brix S, Kristiansen K, Jia H, Ma X

Journal

Molecular psychiatry

Year

2020

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

Experiment 1

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Curated date: 2024/11/08

Curator: KateRasheed

Revision editor(s): KateRasheed

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

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 transplant Response to transplant,response to transplant

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Control Mice (HC Mice)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Schizophrenia Mice (SCZ Mice)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Schizophrenia Mice (SCZ Mice) refers to mice whose gut microbiome was depleted by oral gavage of a cocktail of antibiotics and then re-constructed with gut microbiota from SCZ patients, that is, they were colonized with fecal microbiota of SCZ patients.

Group 0 sample size Number of subjects in the control (unexposed) group: 25

Group 1 sample size Number of subjects in the case (exposed) group: 25

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: WMS

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: BGISEQ-500 Sequencing

Statistical Analysis

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

Statistical test: Kruskall-Wallis

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

Signature 1

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Curated date: 2024/11/08

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Source: Supplementary Table 5

Description: Significantly differentially enriched mOTUs between SCZ mice and HC mice.

Abundance in Group 1: increased abundance in Schizophrenia Mice (SCZ Mice)

NCBI	Quality Control	Links
Aeromonas media
Agrobacterium
Agrobacterium tumefaciens
Anaerotruncus colihominis
Arsenophonus nasoniae
Bordetella pertussis
Fusobacterium ulcerans
Holdemania filiformis
Klebsiella pneumoniae
Legionella jordanis
Neisseria meningitidis serogroup B
Odoribacter splanchnicus
Parabacteroides distasonis
Parabacteroides merdae
Planctomyces
Pseudoflavonifractor capillosus
Pseudomonas sp.
Ruminococcaceae bacterium D16
Shigella sonnei
Treponema denticola
Tuberoidobacter
Vibrio vulnificus
Xanthobacter flavus
[Clostridium] leptum
[Clostridium] scindens

Pseudoalteromonas haloplanktis

Acidocella facilis
Helicobacter acinonychis

Revision editor(s): KateRasheed

Signature 2

Edit History Delete

Mark reviewed

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Curated date: 2024/11/08

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Supplementary Table 5

Description: Significantly differentially enriched mOTUs between SCZ mice and HC mice.

Abundance in Group 1: decreased abundance in Schizophrenia Mice (SCZ Mice)

NCBI	Quality Control	Links
Neisseria elongata
Victivallis vadensis
Paracoccus
Capnocytophaga sp. oral taxon 329
Desulfovibrio sp. 3_1_syn3
Clostridium sp. HGF2
Clostridiales bacterium 1_7_47FAA
Enterocloster bolteae


Klebsiella oxytoca
Parasutterella excrementihominis
Bacteroides caccae
Bacteroides stercoris
Methylococcus capsulatus
Psychrobacter immobilis
Bacteroides uniformis
Segatella copri
Coprobacillus cateniformis
Escherichia coli
Bacteroides clarus
Mycoplasmopsis pulmonis
Clostridioides difficile
Delftia acidovorans
[Clostridium] hylemonae
Helicobacter hepaticus
Lactobacillus johnsonii
Thomasclavelia ramosa
Eggerthella lenta

Revision editor(s): KateRasheed