The oropharyngeal microbiome is altered in individuals with schizophrenia and mania

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Yolken R, Prandovszky E, Severance EG, Hatfield G, Dickerson F
Journal
Schizophrenia research
Year
2020
It is being increasingly recognized that human mucosal surfaces are not sterile but are colonized with microorganisms collectively known as the microbiome. The microbiome can alter brain functioning in humans and animals by way of a series of interactions operative in the brain-immune-gut interactome. We characterized the oropharyngeal microbiome in 316 individuals, including 121 with schizophrenia, 62 with mania, 48 with major depressive disorder, and 85 controls without a psychiatric disorder. We found that the oropharyngeal microflora of individuals with schizophrenia and individuals with mania differed from controls in composition and abundance as measured by the weighted UniFrac distance (both p < .003 adjusted for covariates and multiple comparisons). This measure in individuals with major depressive disorder did not differ from that of controls. We also identified five bacterial taxa which differed among the diagnostic groups. Three of the taxa, Neisseria subflava, Weeksellaceae, and Prevotella, were decreased in individuals with schizophrenia or mania as compared to controls, while Streptococci was increased in these groups. One taxa, Schlegelella, was only found in individuals with mania. Neisseria subflava was also positively associated with cognitive functioning as measured by the Repeatable Battery for the Assessment of Neuropsychological Status. There were no taxa significantly altered in individuals with major depression. Individuals with schizophrenia and mania have altered compositions of the oropharyngeal microbiome. An understanding of the biology of the microbiome and its effect on the brain might lead to new insights into the pathogenesis, and ultimately, the prevention and treatment of these disorders.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
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
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
schizophrenia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients met DSM-IV criteria for schizophrenia, mania participants with symptoms of mania or hypermania could have diagnosis of Bipolar I disorder, single manic episode, most recent episode, mixed Bipolar II episode, most recent episode mixed,or Schizoaffective disorder., bipolar type (manic, hypomanic or mixed state)
Group 0 sample size Number of subjects in the control (unexposed) group
85
Group 1 sample size Number of subjects in the case (exposed) group
121

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

Statistical test
Wald Test
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


Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, race, nicotine dependence, body mass index


Signature 1

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 2, figure 3, figure 4, figure 5, figure 6

Description: Levels of oral microbiome compared to controls adjusted for age, sex, race, cigarette smoking and BMI among individuals with schizophrenia and mania

Abundance in Group 1: increased abundance in schizophrenia

NCBI Links
Streptococcus

Revision editor(s): WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 2, figure 3, figure 4, figure 5, figure 6

Description: Levels of oral microbiome compared to controls adjusted for age, sex, race, cigarette smoking and BMI among individuals with schizophrenia and mania

Abundance in Group 1: decreased abundance in schizophrenia

NCBI Links
Neisseria subflava
Flavobacteriaceae
Prevotella

Revision editor(s): WikiWorks

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
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
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
schizophrenia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients met DSM-IV criteria for schizophrenia, mania participants with symptoms of mania or hypermania could have diagnosis of Bipolar I disorder, single manic episode, most recent episode, mixed Bipolar II episode, most recent episode mixed,or Schizoaffective disorder., bipolar type (manic, hypomanic or mixed state)
Group 0 sample size Number of subjects in the control (unexposed) group
85
Group 1 sample size Number of subjects in the case (exposed) group
62

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Wald Test
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


Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, race, nicotine dependence, body mass index


Signature 1

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 2, figure 3, figure 4, figure 5, figure 6

Description: Levels of oral microbiome compared to controls adjusted for age, sex, race, cigarette smoking and BMI among individuals with schizophrenia and mania

Abundance in Group 1: increased abundance in schizophrenia

NCBI Links
Streptococcus
Schlegelella

Revision editor(s): WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 2, figure 3, figure 4, figure 5, figure 6

Description: Levels of oral microbiome compared to controls adjusted for age, sex, race, cigarette smoking and BMI among individuals with schizophrenia and mania

Abundance in Group 1: decreased abundance in schizophrenia

NCBI Links
Neisseria subflava
Flavobacteriaceae
Prevotella

Revision editor(s): WikiWorks