Epigenetics of the molecular clock and bacterial diversity in bipolar disorder

被引:48
作者
Bengesser, S. A. [1 ]
Moerkl, S. [1 ]
Painold, A. [1 ]
Dalkner, N. [1 ]
Birner, A. [1 ]
Fellendorf, F. T. [1 ]
Platzer, M. [1 ]
Queissner, R. [1 ]
Hamm, C. [1 ]
Maget, A. [1 ]
Pilz, R. [1 ]
Rieger, A. [1 ]
Wagner-Skacel, J. [1 ]
Reininghaus, B. [1 ]
Kapfhammer, H. P. [1 ]
Petek, E. [2 ]
Kashofer, K. [3 ]
Halwachs, B. [3 ]
Holzer, P. [4 ]
Waha, A. [5 ]
Reininghaus, E. Z. [1 ]
机构
[1] MUG, Dept Psychiat & Psychotherapeut Med, Auenbruggerpl 31, A-8036 Graz, Austria
[2] MUG, Diagnost & Res Inst Human Genet, Graz, Austria
[3] MUG, Inst Pathol, Graz, Austria
[4] MUG, Otto Loewi Res Ctr, Graz, Austria
[5] Univ Bonn, Inst Neuropathol, Bonn, Germany
关键词
Gut microbiome; Epigenetics; ARNTL; Bipolar disorder; MB-COMT PROMOTER; GUT MICROBIOME; SCHIZOPHRENIA; GENE; HYPOMETHYLATION; BRAIN; INFLAMMATION; STRESS; SALIVA;
D O I
10.1016/j.psyneuen.2018.11.009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives The gut microbiome harbors substantially more genetic material than our body cells and has an impact on a huge variety of physiological mechanisms including the production of neurotransmitters and the interaction with brain functions through the gut-brain-axis. Products of microbiota can affect methylation according to preclinical studies. The current investigation aimed at analyzing the correlation between gut microbiome diversity and the methylation of the clock gene ARNTL in individuals with Bipolar Disorder (BD). Methods Genomic DNA was isolated from fasting blood of study participants with BD (n = 32). The methylation analysis of the ARNTL CG site cg05733463 was performed by bisulfite treatment of genomic DNA with the Epitect kit, PCR and pyrosequencing. Additionally, DNA was extracted from stool samples and subjected to 16S rRNA sequencing. QIIME was used to analyze microbiome data. Results Methylation status of the ARNTL CpG position cg05733463 correlated significantly with bacterial diversity (Simpson index: r=-0.389, p=0.0238) and evenness (Simpson evenness index: r=-0.358, p=0.044). Furthermore, bacterial diversity differed significantly between euthymia and depression (F(1,30) =4.695, p=0.039). Discussion The results of our pilot study show that bacterial diversity differs between euthymia and depression. Interestingly, gut microbiome diversity and evenness correlate negatively with methylation of ARNTL, which is known to regulate monoamine oxidase A transcription. We propose that alterations in overall diversity of the gut microbiome represent an internal environmental factor that has an epigenetic impact on the clock gene ARNTL which is thought to be involved in BD pathogenesis.
引用
收藏
页码:160 / 166
页数:7
相关论文
共 49 条
[1]   Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder [J].
Abdolmaleky, Hamid Mostafavi ;
Cheng, Kuang-hung ;
Faraone, Stephen V. ;
Wilcox, Marsha ;
Glatt, Stephen J. ;
Gao, Fangming ;
Smith, Cassandra L. ;
Shafa, Rahim ;
Aeali, Batol ;
Carnevale, Julie ;
Pan, Hongjie ;
Papageorgis, Panagiotis ;
Ponte, Jose F. ;
Sivaraman, Vadivelu ;
Tsuang, Ming T. ;
Thiagalingam, Sam .
HUMAN MOLECULAR GENETICS, 2006, 15 (21) :3132-3145
[2]   Microbiome, inflammation, epigenetic alterations, and mental diseases [J].
Alam, Reza ;
Abdolmaleky, Hamid M. ;
Zhou, Jin-Rong .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2017, 174 (06) :651-660
[3]   Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder A Genome-Wide Association Study [J].
Amare, Azmeraw T. ;
Schubert, Klaus Oliver ;
Hou, Liping ;
Clark, Scott R. ;
Papiol, Sergi ;
Heilbronner, Urs ;
Degenhardt, Franziska ;
Tekola-Ayele, Fasil ;
Hsu, Yi-Hsiang ;
Shekhtman, Tatyana ;
Adli, Mazda ;
Akula, Nirmala ;
Akiyama, Kazufumi ;
Ardau, Raffaella ;
Arias, Barbara ;
Aubry, Jean-Michel ;
Backlund, Lena ;
Bhattacharjee, Abesh Kumar ;
Bellivier, Frank ;
Benabarre, Antonio ;
Bengesser, Susanne ;
Biernacka, Joanna M. ;
Birner, Armin ;
Brichant-Petitjean, Clara ;
Cervantes, Pablo ;
Chen, Hsi-Chung ;
Chillotti, Caterina ;
Cichon, Sven ;
Cruceanu, Cristiana ;
Czerski, Piotr M. ;
Dalkner, Nina ;
Dayer, Alexandre ;
Del Zompo, Maria ;
DePaulo, J. Raymond ;
Etain, Bruno ;
Falkai, Peter ;
Forstner, Andreas J. ;
Frisen, Louise ;
Frye, Mark A. ;
Fullerton, Janice M. ;
Gard, Sebastien ;
Garnham, Julie S. ;
Goes, Fernando S. ;
Grigoroiu-Serbanescu, Maria ;
Grof, Paul ;
Hashimoto, Ryota ;
Hauser, Joanna ;
Herms, Stefan ;
Hoffmann, Per ;
Hofmann, Andrea .
JAMA PSYCHIATRY, 2018, 75 (01) :65-74
[4]   Oxidative stress markers in bipolar disorder: A meta-analysis [J].
Andreazza, Ana C. ;
Kauer-Sant'Anna, Marcia ;
Frey, Benicio N. ;
Bond, David J. ;
Kapczinski, Flavio ;
Young, L. Trevor ;
Yatham, Lakshmi N. .
JOURNAL OF AFFECTIVE DISORDERS, 2008, 111 (2-3) :135-144
[5]  
BENGESSER S., 2013, GENETICS BIPOLAR DIS
[6]   Is the molecular clock ticking differently in bipolar disorder? Methylation analysis of the clock gene ARNTL [J].
Bengesser, Susanne A. ;
Reininghaus, Eva Z. ;
Lackner, Nina ;
Birner, Armin ;
Fellendorf, Frederike T. ;
Platzer, Martina ;
Kainzbauer, Nora ;
Tropper, Bernhard ;
Hoermanseder, Christa ;
Queissner, Robert ;
Kapfhammer, Hans-Peter ;
Wallner-Liebmann, Sandra J. ;
Fuchs, Robert ;
Petek, Erwin ;
Windpassinger, Christian ;
Schnalzenberger, Mario ;
Reininghaus, Bernd ;
Evert, Bernd ;
Waha, Andreas .
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, 2018, 19 :S21-S29
[7]   Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors [J].
Berk, M. ;
Kapczinski, F. ;
Andreazza, A. C. ;
Dean, O. M. ;
Giorlando, F. ;
Maes, M. ;
Yuecel, M. ;
Gama, C. S. ;
Dodd, S. ;
Dean, B. ;
Magalhaes, P. V. S. ;
Amminger, P. ;
McGorry, P. ;
Malhi, G. S. .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2011, 35 (03) :804-817
[8]   Life events and social rhythms in bipolar spectrum disorders: An examination of social rhythm sensitivity [J].
Boland, Elaine M. ;
Bender, Rachel E. ;
Alloy, Lauren B. ;
Conner, Bradley T. ;
LaBelle, Denise R. ;
Abramson, Lyn Y. .
JOURNAL OF AFFECTIVE DISORDERS, 2012, 139 (03) :264-272
[9]   Fast, accurate error-correction of amplicon pyrosequences using Acacia [J].
Bragg, Lauren ;
Stone, Glenn ;
Imelfort, Michael ;
Hugenholtz, Philip ;
Tyson, Gene W. .
NATURE METHODS, 2012, 9 (05) :425-426
[10]   QIIME allows analysis of high-throughput community sequencing data [J].
Caporaso, J. Gregory ;
Kuczynski, Justin ;
Stombaugh, Jesse ;
Bittinger, Kyle ;
Bushman, Frederic D. ;
Costello, Elizabeth K. ;
Fierer, Noah ;
Pena, Antonio Gonzalez ;
Goodrich, Julia K. ;
Gordon, Jeffrey I. ;
Huttley, Gavin A. ;
Kelley, Scott T. ;
Knights, Dan ;
Koenig, Jeremy E. ;
Ley, Ruth E. ;
Lozupone, Catherine A. ;
McDonald, Daniel ;
Muegge, Brian D. ;
Pirrung, Meg ;
Reeder, Jens ;
Sevinsky, Joel R. ;
Tumbaugh, Peter J. ;
Walters, William A. ;
Widmann, Jeremy ;
Yatsunenko, Tanya ;
Zaneveld, Jesse ;
Knight, Rob .
NATURE METHODS, 2010, 7 (05) :335-336