Interaction Between Atypical Antipsychotics and the Gut Microbiome in a Bipolar Disease Cohort

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

28035686

DOI Digital object identifier for electronic documents.

10.1002/phar.1890

URI

Authors

Flowers SA, Evans SJ, Ward KM, McInnis MG, Ellingrod VL

Journal

Pharmacotherapy

Year

2017

Keywords:

atypical antipsychotics, metabolic disease, microbiome

OBJECTIVES: The atypical antipsychotic (AAP) class is often associated with metabolic disease, but the mechanistic underpinnings of this risk are not understood. Due to reports linking gut bacteria function to metabolic disease, we hypothesize that AAP treatment in adults results in gut dysbiosis potentiating metabolic criteria. This report describes recent findings linking AAP treatment with differences in gut microbiota communities in a human cohort with bipolar disorder (BD). METHODS: In a cross-sectional design, we obtained 16S ribosomal sequences from 117 BD patients (49 AAP treated, 68 non-AAP treated). Analysis of molecular variance (AMOVA) was used to detect significant clustering of microbial communities between groups, and the inverse Simpson Diversity Index was used to calculate alpha diversity. Detection of differentially abundant operational taxonomic units (OTUs) between groups was performed using linear discriminant analysis effect size. RESULTS: The AAP-treated cohort was significantly younger and had an increased body mass index compared with non-AAP-treated patients. Groups did not differ in other psychotropic medication use with the exception of higher use of benzodiazepines in the AAP cohort. We detected significant separation between microbiota communities of AAP-treated and nontreated patients (AMOVA; p=0.04). AAP-treated females showed significant decreased species diversity when compared with non-AAP-treated females (p=0.015). Males showed no significant diversity between treatment groups (p=0.8). Differentially abundant OTUs between treatment groups were OTU1, OTU25, and OTU32 that classified to Lachnospiraceae, Akkermansia, and Sutterella, respectively. CONCLUSIONS: These data suggest that AAP treatment is associated with specific representation of gut bacterial families in AAP-treated patients. In addition, AAP treatment is associated with decreased species richness in female AAP-treated patients.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects: United States of America

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: Bipolar disorder [X]Bipolar affective disorder, unspecified,[X]Bipolar affective disorder, unspecified (disorder),Affective Bipolar Psychosis,Affective Psychosis, Bipolar,Bipolar affective disorder,bipolar affective disorder,Bipolar affective disorder , current episode mixed (disorder),Bipolar affective disorder, current episode depression (disorder),Bipolar affective disorder, manic, unspecified degree,Bipolar affective disorder, mixed, unspecified degree,Bipolar Affective Psychosis,Bipolar Depression,bipolar depression,BIPOLAR DIS,bipolar disease,bipolar disorder,Bipolar disorder (disorder),bipolar disorder manic phase,BIPOLAR DISORDER NOS,Bipolar disorder, NOS,Bipolar disorder, unspecified,Bipolar Disorders,Depression, Bipolar,Depressive-manic psych.,depressive-manic psych.,Disorder, Bipolar,Disorder, Manic,MAFD,major affective disorder,major bipolar affective disorder,Mania,Manias,Manic Bipolar Affective disorder,manic bipolar affective disorder,Manic bipolar I disorder,manic bipolar I disorder,Manic bipolar I disorder (disorder),manic depression,Manic Depressive disorder,manic depressive disorder,MANIC DEPRESSIVE ILLNESS,Manic Depressive Psychosis,MANIC DIS,Manic Disorder,manic disorder,Manic Disorders,Manic State,Manic States,Manic-Depression,manic-depression,Manic-depressive illness,manic-depressive illness,Manic-Depressive Psychoses,Manic-depressive psychosis,manic-depressive psychosis,Manic-depressive syndrome NOS,MDI - Manic-depressive illness,mixed bipolar affective disorder (disorder),mixed bipolar affective disorder, NOS (disorder),mixed bipolar disorder,mixed bipolar I disorder (disorder),Psychoses, Bipolar Affective,Psychoses, Manic Depressive,Psychoses, Manic-Depressive,Psychosis, Bipolar Affective,Psychosis, Manic Depressive,Psychosis, Manic-Depressive,State, Manic,States, Manic,Unspecified bipolar affective disorder,Unspecified bipolar affective disorder (disorder),Unspecified bipolar affective disorder, NOS,Unspecified bipolar affective disorder, NOS (disorder),Unspecified bipolar affective disorder, unspecified,Unspecified bipolar affective disorder, unspecified (disorder),Bipolar disorder

Group 0 name Corresponds to the control (unexposed) group for case-control studies: non users

Group 1 name Corresponds to the case (exposed) group for case-control studies: atypical antipsychotic users

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Medication group was defined by the use of an Atypical Antipsychotics at the time of fecal sample collection

Group 0 sample size Number of subjects in the control (unexposed) group: 68

Group 1 sample size Number of subjects in the case (exposed) group: 49

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: Linear Regression

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)?: No

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

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Signature 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure3

Description: Differentially abundant members of gut microbiota in bipolar disorder (BD) patients treated with atypical antipsychotics (AAP)

Abundance in Group 1: increased abundance in atypical antipsychotic users

NCBI	Quality Control	Links
Lachnospiraceae

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Signature 2

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure3

Description: Differentially abundant members of gut microbiota in bipolar disorder (BD) patients treated with atypical antipsychotics (AAP)

Abundance in Group 1: decreased abundance in atypical antipsychotic users

NCBI	Quality Control	Links
Akkermansia

Revision editor(s): WikiWorks