Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders

Introduction: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. Methods: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. Results: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). Conclusion: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

[1]  H. Sokol,et al.  Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands , 2022, Gut microbes.

[2]  A. Kardinaal,et al.  Probiotics, prebiotics and postbiotics for better sleep quality: a narrative review. , 2022, Beneficial microbes.

[3]  X. Pang,et al.  Chronic intermittent hypoxia induces gut microbial dysbiosis and infers metabolic dysfunction in mice. , 2022, Sleep medicine.

[4]  Y. Bao,et al.  Alterations of the Gut Microbiota in Response to Total Sleep Deprivation and Recovery Sleep in Rats , 2022, Nature and science of sleep.

[5]  S. Kulling,et al.  Metabolism of Daidzein and Genistein by Gut Bacteria of the Class Coriobacteriia , 2021, Foods.

[6]  Ana Rita Brochado,et al.  Bioaccumulation of therapeutic drugs by human gut bacteria , 2021, Nature.

[7]  K. O'Halloran,et al.  Microbiota and sleep: awakening the gut feeling. , 2021, Trends in molecular medicine.

[8]  Huimei An,et al.  Gut Microbiome Composition Associated With Major Depressive Disorder and Sleep Quality , 2021, Frontiers in Psychiatry.

[9]  G. Grosso Nutritional Psychiatry: How Diet Affects Brain through Gut Microbiota , 2021, Nutrients.

[10]  Kuo-Hu Chen,et al.  Utilization of Isoflavones in Soybeans for Women with Menopausal Syndrome: An Overview , 2021, International journal of molecular sciences.

[11]  S. Watson,et al.  Sleep and Circadian Rhythm Disorder in Bipolar Affective Disorder. , 2021, Current topics in behavioral neurosciences.

[12]  A. Kraeuter,et al.  The Gut Microbiome in Psychosis From Mice to Men: A Systematic Review of Preclinical and Clinical Studies , 2020, Frontiers in Psychiatry.

[13]  J. Espín,et al.  Metabolism of different dietary phenolic compounds by the urolithin-producing human-gut bacteria Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciens. , 2020, Food & function.

[14]  Mary I. Butler,et al.  Sleep and Microbiome in Psychiatric Diseases , 2020, Nutrients.

[15]  V. Giridharan,et al.  The role of the microbiota-gut-brain axis in neuropsychiatric disorders , 2020, Revista brasileira de psiquiatria.

[16]  V. Jala,et al.  Microbial Metabolite Urolithin B Inhibits Recombinant Human Monoamine Oxidase A Enzyme , 2020, Metabolites.

[17]  C. Irwin,et al.  Effects of probiotics and paraprobiotics on subjective and objective sleep metrics: a systematic review and meta-analysis , 2020, European Journal of Clinical Nutrition.

[18]  Brittany A. Matenchuk,et al.  Sleep, circadian rhythm, and gut microbiota. , 2020, Sleep medicine reviews.

[19]  Rob Knight,et al.  QIIME 2 Enables Comprehensive End‐to‐End Analysis of Diverse Microbiome Data and Comparative Studies with Publicly Available Data , 2020, Current protocols in bioinformatics.

[20]  T. Dinan,et al.  The role of the gut microbiome in the development of schizophrenia , 2020, Schizophrenia Research.

[21]  A. Flatt,et al.  Self-reported sleep quality is associated with gut microbiome composition in young, healthy individuals: a pilot study. , 2020, Sleep medicine.

[22]  H. Blottière,et al.  SCFA: mechanisms and functional importance in the gut , 2020, Proceedings of the Nutrition Society.

[23]  R. Knight,et al.  Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome , 2020, PloS one.

[24]  A. Iwanami,et al.  Gut microbiota and major depressive disorder: A systematic review and meta-analysis. , 2020, Journal of affective disorders.

[25]  Lauren D Asarnow,et al.  Depression and sleep: what has the treatment research revealed and could the HPA axis be a potential mechanism? , 2019, Current opinion in psychology.

[26]  Zheng-wu Peng,et al.  Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. , 2019, Journal of affective disorders.

[27]  Cole G Easson,et al.  Gut microbiome diversity is associated with sleep physiology in humans , 2019, PloS one.

[28]  S. Chong,et al.  Prevalence and correlates of sleep disorder symptoms in psychiatric disorders , 2019, Psychiatry Research.

[29]  S. Carding,et al.  Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health , 2019, Gut microbes.

[30]  M. Irwin Sleep and inflammation: partners in sickness and in health , 2019, Nature Reviews Immunology.

[31]  Cory R. Theberge,et al.  Gut Microbiome: Profound Implications for Diet and Disease , 2019, Kompass Nutrition & Dietetics.

[32]  B. Vervliet,et al.  The role of short-chain fatty acids in microbiota–gut–brain communication , 2019, Nature Reviews Gastroenterology & Hepatology.

[33]  L. Kapás,et al.  Butyrate, a metabolite of intestinal bacteria, enhances sleep , 2019, Scientific Reports.

[34]  L. Kuller,et al.  Effect of S-equol and Soy Isoflavones on Heart and Brain , 2019, Current cardiology reviews.

[35]  B. Fiebich,et al.  Induction of Autophagy and Activation of SIRT-1 Deacetylation Mechanisms Mediate Neuroprotection by the Pomegranate Metabolite Urolithin A in BV2 Microglia and Differentiated 3D Human Neural Progenitor Cells. , 2019, Molecular nutrition & food research.

[36]  M. Lai,et al.  Exploration of microbiota targets for major depressive disorder and mood related traits. , 2019, Journal of psychiatric research.

[37]  Liping Xu,et al.  Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice , 2019, Journal of Neuroinflammation.

[38]  B. Stecher,et al.  Sequence and cultivation study of Muribaculaceae reveals novel species, host preference, and functional potential of this yet undescribed family , 2019, Microbiome.

[39]  Peng Xie,et al.  The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice , 2019, Science Advances.

[40]  D. Jeste,et al.  Differences in gut microbiome composition between persons with chronic schizophrenia and healthy comparison subjects , 2019, Schizophrenia Research.

[41]  M. Ota,et al.  Bifidobacterium and Lactobacillus Counts in the Gut Microbiota of Patients With Bipolar Disorder and Healthy Controls , 2019, Front. Psychiatry.

[42]  F. Fan,et al.  The Role of Microbiome in Insomnia, Circadian Disturbance and Depression , 2018, Front. Psychiatry.

[43]  T. Dinan,et al.  Schizophrenia and the microbiome: Time to focus on the impact of antipsychotic treatment on the gut microbiota , 2018, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[44]  M. Hattori,et al.  The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study. , 2018, Journal of affective disorders.

[45]  Karl Kashofer,et al.  A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode , 2018, Bipolar disorders.

[46]  Songnian Hu,et al.  Analysis of gut microbiota diversity and auxiliary diagnosis as a biomarker in patients with schizophrenia: A cross-sectional study , 2018, Schizophrenia Research.

[47]  G. Belcaro,et al.  Improvement in mood, oxidative stress, fatigue, and insomnia following supplementary management with Robuvit®. , 2018, Journal of neurosurgical sciences.

[48]  Xiaoli Wu,et al.  Recognizing Depression from the Microbiota–Gut–Brain Axis , 2018, International journal of molecular sciences.

[49]  Jingyuan Fu,et al.  Pharmacomicrobiomics: a novel route towards personalized medicine? , 2018, Protein & Cell.

[50]  Gregor Hasler,et al.  Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders , 2018, Front. Psychiatry.

[51]  R. Delorme,et al.  Insomnia and hypersomnia in major depressive episode: Prevalence, sociodemographic characteristics and psychiatric comorbidity in a population-based study. , 2018, Journal of affective disorders.

[52]  F. Ferrarelli,et al.  Schizophrenia and sleep disorders: links, risks, and management challenges , 2017, Nature and science of sleep.

[53]  C. Dutta,et al.  Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity , 2017, Front. Microbiol..

[54]  Shervin Assari,et al.  The gut microbiome composition associates with bipolar disorder and illness severity. , 2017, Journal of psychiatric research.

[55]  P. Gallagher,et al.  Sleep and circadian rhythm disturbance in bipolar disorder , 2017, Psychological Medicine.

[56]  G. Corbi,et al.  Influence of equol and resveratrol supplementation on health-related quality of life in menopausal women: A randomized, placebo-controlled study. , 2017, Maturitas.

[57]  T. Dinan,et al.  Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. , 2016, Journal of psychiatric research.

[58]  Paul J. McMurdie,et al.  DADA2: High resolution sample inference from Illumina amplicon data , 2016, Nature Methods.

[59]  J Licinio,et al.  From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways , 2016, Molecular Psychiatry.

[60]  William A. Walters,et al.  Improved Bacterial 16S rRNA Gene (V4 and V4-5) and Fungal Internal Transcribed Spacer Marker Gene Primers for Microbial Community Surveys , 2015, mSystems.

[61]  T. Kanai,et al.  The gut microbiota and inflammatory bowel disease , 2014, Seminars in Immunopathology.

[62]  M. Tomita,et al.  Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells , 2013, Nature.

[63]  A. O'Neil,et al.  The association between diet quality, dietary patterns and depression in adults: a systematic review , 2013, BMC Psychiatry.

[64]  K. Katoh,et al.  MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability , 2013, Molecular biology and evolution.

[65]  T. Dinan,et al.  Mind-altering Microorganisms: the Impact of the Gut Microbiota on Brain and Behaviour , 2022 .

[66]  Emeran A. Mayer,et al.  Gut feelings: the emerging biology of gut–brain communication , 2011, Nature Reviews Neuroscience.

[67]  K. Setchell,et al.  Neuromodulation by soy diets or equol: Anti-depressive & anti-obesity-like influences, age- & hormone-dependent effects , 2011, BMC Neuroscience.

[68]  Paramvir S. Dehal,et al.  FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments , 2010, PloS one.

[69]  Harry J. Flint,et al.  Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. , 2009, FEMS microbiology letters.

[70]  M. Opp,et al.  How (and why) the immune system makes us sleep , 2009, Nature Reviews Neuroscience.

[71]  I. Antonijevic HPA axis and sleep: Identifying subtypes of major depression , 2008, Stress.

[72]  M. Fava,et al.  Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression. , 2007, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[73]  R. Armitage Sleep and circadian rhythms in mood disorders , 2007, Acta psychiatrica Scandinavica. Supplementum.

[74]  M. Fava,et al.  Eszopiclone Co-Administered With Fluoxetine in Patients With Insomnia Coexisting With Major Depressive Disorder , 2006, Biological Psychiatry.

[75]  Eoin L. Brodie,et al.  Greengenes: Chimera-checked 16S rRNA gene database and workbench compatible in ARB , 2006 .

[76]  A. Barsevick,et al.  Psychometric evaluation of the Pittsburgh Sleep Quality Index in cancer patients. , 2004, Journal of pain and symptom management.

[77]  N. Andreasen,et al.  Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia. , 2002, Comprehensive psychiatry.

[78]  M. Andrykowski,et al.  Psychometric evaluation of the Pittsburgh Sleep Quality Index. , 1998, Journal of psychosomatic research.

[79]  R. Zafonte,et al.  Insomnia Screening in Postacute Traumatic Brain Injury: Utility and Validity of the Pittsburgh Sleep Quality Index , 1998, American journal of physical medicine & rehabilitation.

[80]  Daniel J Buysse,et al.  The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research , 1989, Psychiatry Research.

[81]  J. Ward Sleep and psychiatric disorder. , 1968, Canadian Psychiatric Association journal.

[82]  E. C. Pielou The measurement of diversity in different types of biological collections , 1966 .

[83]  A. Cleare,et al.  Perturbations in gut microbiota composition in psychiatric disorders: a review and meta­analysis , 2022 .

[84]  H. Flint,et al.  Formation of propionate and butyrate by the human colonic microbiota. , 2017, Environmental microbiology.

[85]  A. Krystal,et al.  Sleep disturbance in psychiatric disorders: effects on function and quality of life in mood disorders, alcoholism, and schizophrenia. , 2008, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[86]  Sang Joon Kim,et al.  A Mathematical Theory of Communication , 2006 .

[87]  A. Harvey,et al.  Sleep-related functioning in euthymic patients with bipolar disorder, patients with insomnia, and subjects without sleep problems. , 2005, The American journal of psychiatry.

[88]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[89]  D. Faith Conservation evaluation and phylogenetic diversity , 1992 .