Gut microbiota composition in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives

Study information

Reviewed Marked as Reviewed by Folakunmi on 2024-2-21

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

30261302

DOI Digital object identifier for electronic documents.

10.1016/j.bbi.2018.09.026

URI

Authors

Coello K, Hansen TH, Sørensen N, Munkholm K, Kessing LV, Pedersen O, Vinberg M

Journal

Brain, behavior, and immunity

Year

2019

Keywords:

Bipolar disorder, Gut microbiota, Microbiota, Newly diagnosed, Unaffected relatives

OBJECTIVE: An aberrant gut microbiota may be associated with a broad spectrum of diseases including mental illness. The gut microbiota is scarcely studied in bipolar disorder (BD). We examined the gut microbiota composition in patients with newly diagnosed BD, their unaffected first-degree relatives and healthy individuals. METHODS: Stool samples were collected from 113 patients with BD, 39 unaffected first-degree relatives and 77 healthy individuals and the microbiota was profiled using 16S rRNA gene amplicon sequencing. RESULTS: The gut microbiota community membership of patients with BD differed from that of healthy individuals (R2 = 1.0%, P = 0.008), whereas the community membership of unaffected first-degree relatives did not. Flavonifractor was present in 61% of patients with BD, 42% of their unaffected relatives and 39% of healthy individuals. Presence of Flavonifractor was associated with an odds ratio of 2.9 (95%CI: 1.6-5.2, P = 5.8 × 10-4, Q = 0.036) for having BD. When excluding smokers, presence of Flavonifractor was associated with an odds ratio of 2.3 (95%CI: 1.1-5.3, P = 0.019) for having BD. However, when considering the subsample of non-smokers only, BD and presence of Flavonifractor were no longer associated when adjusted for all possible tests at genus level (Q = 0.6). Presence of Flavonifractor in patients with BD was associated with smoking and female sex, but not with age, waist circumference, exercise level, high-sensitive C-reactive protein, current affective state, subtype of BD, illness duration or psychotropic medication, respectively. CONCLUSION: Flavonifractor, a bacterial genus that may induce oxidative stress and inflammation in its host, was associated with BD. Higher prevalence of smoking among patients with BD contributed to our findings, and it cannot be excluded that findings are influenced by residual confounding.

Experiment 1

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Subjects

Location of subjects: Denmark

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: healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: bipolar disorder patients

Group 0 sample size Number of subjects in the control (unexposed) group: 77

Group 1 sample size Number of subjects in the case (exposed) group: 113

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: Fisher's Exact 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, physical activity, smoking behavior, waist circumference, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Richness Number of species: unchanged

Signature 1

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Source: table 2, figure3

Description: gut microbiota composition in patients with newly diagnosed bipolar and healthy controls

Abundance in Group 1: increased abundance in bipolar disorder patients

NCBI	Quality Control	Links
Flavonifractor

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Experiment 2

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Differences from previous experiment shown

Subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Healthy first degree relatives of bipolar disorder patients