title: The gut microbiome composition associates with bipolar disorder and illness severity.
abstract: The gut microbiome is emerging as an important factor in regulating mental health yet it remains unclear what the target should be for psychiatric treatment. We aimed to elucidate the complement of the gut-microbiome community for individuals with bipolar disorder relative to controls; and test for relationships with burden of disease measures. We compared the stool microbiome from individuals with bipolar disorder (n = 115) and control subjects (n = 64) using 16S ribosomal RNA (rRNA) gene sequence analysis. Analysis of molecular variance (AMOVA) revealed global community case-control differences (AMOVA p = 0.047). Operational Taxonomical Unit (OTU) level analysis revealed significantly decreased fractional representation (p < 0.001) of Faecalibacterium after adjustment for age, sex, BMI and false discovery rate (FDR) correction at the p < 0.05 level. Within individuals with bipolar disorder, the fractional representation of Faecalibacterium associated with better self-reported health outcomes based on the Short Form Health Survey (SF12); the Patient Health Questionnaire (PHQ9); the Pittsburg Sleep Quality Index (PSQI); the Generalized Anxiety Disorder scale (GAD7); and the Altman Mania Rating Scale (ASRM), independent of covariates. This study provides the first detailed analysis of the gut microbiome relationships with multiple psychiatric domains from a bipolar population. The data support the hypothesis that targeting the microbiome may be an effective treatment paradigm for bipolar disorder.
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States. Electronic address: evanssi@umich.edu.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Evans
authors.affiliation: Department of Internal Medicine/Infectious Diseases Division, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Bassis
authors.affiliation: Department of Internal Medicine/Infectious Diseases Division, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Hein
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Shervin
authors.initials: S
authors.lastname: Assari
authors.affiliation: School of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Flowers
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Marisa B
authors.initials: MB
authors.lastname: Kelly
authors.affiliation: Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, United States; Department of Internal Medicine/Infectious Diseases Division, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Vince B
authors.initials: VB
authors.lastname: Young
authors.affiliation: School of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Vicky E
authors.initials: VE
authors.lastname: Ellingrod
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000382:microbiology* / Q000503:physiopathology*; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D012044:Regression Analysis; D011795:Surveys and Questionnaires
chemical_list: D012336:RNA, Ribosomal, 16S
keywords: Bipolar disorder; Faecalibacterium; Generalized Anxiety Disorder scale; Microbiome; Patient Health Questionnaire; Pittsburg Sleep Quality Index