Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study

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Reviewed Marked as Reviewed by Atrayees on 2023-6-5
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Ling Z, Jin G, Yan X, Cheng Y, Shao L, Song Q, Liu X, Zhao L
Journal
Frontiers in cellular and infection microbiology
Year
2022
Keywords:
Faecalibacterium, LEfSe, Schizophrenia, dysbiosis, non-invasive diagnosis
Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial β-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium, Roseburia, Actinomyces, Butyricicoccus, Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1β were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-6-5

Curated date: 2023/03/09

Curator: Dupe

Revision editor(s): Dupe

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 control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Elderly Schizophrenia Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Elderly Schizophrenia Patients
Group 0 sample size Number of subjects in the control (unexposed) group
71
Group 1 sample size Number of subjects in the case (exposed) group
90
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
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-5

Curated date: 2023/03/10

Curator: Dupe

Revision editor(s): Dupe, Aiyshaaaa, Atrayees

Source: Figure 2A

Description: Differential LEfSe- associated bacterial taxa between the elderly SZ patients and the healthy controls

Abundance in Group 1: increased abundance in Elderly Schizophrenia Patients

NCBI Quality ControlLinks
Actinomycetota
Aeromonadales
Akkermansia
Alloprevotella
Bacteroidia
Bifidobacteriaceae
Bifidobacterium
Bilophila
Catenibacterium
Coriobacteriaceae
Desulfovibrio
Desulfovibrionaceae
Desulfovibrionales
Erysipelotrichaceae
Erysipelotrichales
Fusobacteriaceae
Fusobacterium
Holdemanella
Megamonas
Mitsuokella
Peptostreptococcaceae
Prevotellaceae
Romboutsia
Senegalimassilia
Slackia
Streptococcaceae
Streptococcus
Succinivibrio
Sutterella
Synergistota
Verrucomicrobiota
unclassified Bacteroidales
unclassified Coriobacteriaceae
unclassified Porphyromonadaceae

Revision editor(s): Dupe, Aiyshaaaa, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-5

Curated date: 2023/03/10

Curator: Dupe

Revision editor(s): Dupe, Atrayees

Source: Figure 2A

Description: Differential LEfSe- associated bacterial taxa between the elderly SZ patients and the healthy controls

Abundance in Group 1: decreased abundance in Elderly Schizophrenia Patients

NCBI Quality ControlLinks
Anaerostipes
Bacilli
Bacillota
Butyricicoccus
Citrobacter
Coprococcus
Eisenbergiella
Eubacteriales
Faecalibacterium
Fusicatenibacter
Fusicatenibacter saccharivorans
Gemmiger
Klebsiella
Lachnospiraceae
Lactobacillales
Parasutterella
Roseburia
Ruminococcus
Turicibacter
unclassified Lachnospiraceae
Oscillospiraceae

Revision editor(s): Dupe, Atrayees

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-6-5

Curated date: 2023/03/11

Curator: Dupe

Revision editor(s): Dupe, Atrayees

Differences from previous experiment shown

Subjects

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

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-5

Curated date: 2023/03/11

Curator: Dupe

Revision editor(s): Dupe

Source: Figure 2B

Description: the mean relative abundances of bacterial taxa in SZ patients and healthy control from phylum to genus level

Abundance in Group 1: increased abundance in Schizophrenia

NCBI Quality ControlLinks
Acidaminococcaceae
Acidaminococcus
Actinomyces
Actinomycetaceae
Actinomycetota
Akkermansia
Alloprevotella
Atopobium
Bacteroidia
Bilophila
Catenibacterium
Collinsella
Coriobacteriaceae
Corynebacteriaceae
Corynebacterium
Desulfovibrio
Desulfovibrionaceae
Dorea
Erysipelotrichaceae
Fusobacteriia
Haemophilus
Halomonadaceae
Halomonas
Holdemanella
Hyphomicrobiaceae
Hyphomonadaceae
Megamonas
Megasphaera
Micrococcaceae
Olsenella
Paracoccaceae
Parvimonas
Pasteurellaceae
Pelagibacterium
Peptostreptococcaceae
Phascolarctobacterium
Phyllobacteriaceae
Prevotella
Prevotellaceae
Romboutsia
Senegalimassilia
Staphylococcaceae
Streptococcaceae
Streptococcus
Succinivibrio
Succinivibrionaceae
Sutterella
Synergistaceae
Synergistota
Verrucomicrobiaceae
Verrucomicrobiota
Lysobacteraceae

Revision editor(s): Dupe

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-5

Curated date: 2023/03/11

Curator: Dupe

Revision editor(s): Dupe, Atrayees

Source: Figure 2B

Description: the mean relative abundances of bacterial taxa in SZ patients and healthy control from phylum to genus level

Abundance in Group 1: decreased abundance in Schizophrenia

NCBI Quality ControlLinks
Bacillota
Butyricicoccus
Coprococcus
Faecalibacterium
Fusicatenibacter
Gemmiger
Lachnospiraceae
Pseudomonadota
Roseburia
Oscillospiraceae

Revision editor(s): Dupe, Atrayees