Overview and systematic review of studies of microbiome in schizophrenia and bipolar disorder

https://doi.org/10.1016/j.jpsychires.2018.01.013Get rights and content

Abstract

Schizophrenia and bipolar disorder are among the leading causes of disability, morbidity, and mortality worldwide. In addition to being serious mental illnesses, these disorders are associated with considerable systemic physiological dysfunction, including chronic inflammation and elevated oxidative stress. The advent of sophisticated sequencing techniques has led to a growing interest in the potential role of gut microbiota in human health and disease. Advances in this area have transformed our understanding of a number of medical conditions and have generated a new perspective suggesting that gut microbiota might be involved in the development and maintenance of brain/mental health. Animal models have demonstrated strong though indirect evidence for a contributory role of intestinal microbiota in psychiatric symptomatology and have linked the microbiome with neuropsychiatric conditions. We present a systematic review of clinical studies of microbiome in schizophrenia and bipolar disorder. The published literature has a number of limitations; however, the investigations suggest that these disorders are associated with reduced microbial diversity and show global community differences compared to non-psychiatric comparison samples. In some reports, specific microbial taxa were associated with clinical disease characteristics, including physical health, depressive and psychotic symptoms, and sleep, but little information on the functional potential of those community changes. Studies also suggest increased intestinal inflammation and permeability, which may be among the principal mechanisms by which microbial dysbiosis impacts systemic physiological functioning. We highlight gaps in the current literature and implications for diagnosis and therapeutic interventions, and outline future directions for microbiome research in psychiatry.

Section snippets

Why microbiome?

The microbiome is a dynamic ecological community of microorganisms and their genes, including mainly bacteria, but also archaea, microbial eukaryotes, fungi, and viruses that inhabit the human body. For decades, the importance of the human microbiome remained elusive, due to technical challenges in studying unculturable microorganisms (Pace, 1997, Qin et al., 2010, Sogin et al., 1972, Woese and Fox, 1977). Only with the advent of high-throughput sequencing techniques has it become apparent that

Preclinical studies of the microbiome in neuropsychiatric disorders

In this ever-expanding field, researchers are now investigating how the intestinal microbiota influence distal sites, particularly the brain. In psychiatric disorders, the gut microbiome has been of particular interest because it plays a significant role in brain function and behavior (Diaz Heijtz et al., 2011), which has led to coining of the term “gut-brain axis.” The mechanisms by which peripheral intestinal microorganisms are linked to emotional and cognitive functions of the brain are not

A systematic review of clinical studies of the microbiome in schizophrenia and bipolar disorder

We conducted a systematic review of studies of the microbiome in patients with schizophrenia and BD. We searched PubMed, PsycINFO, and Embase for articles published before May 3, 2017 using the following search string: microbiome AND (schizophrenia OR psychosis OR bipolar OR severe mental illness). We considered studies that utilized high-throughput sequencing methods to characterize microorganisms in individuals clinically diagnosed with schizophrenia, schizoaffective disorder, BD, or related

Conclusions and perspectives

Schizophrenia and BD are heterogeneous diseases with multiple plausible pathophysiological contributors. Abundant evidence points to the immune system as an important factor in the pathogenesis and developmental trajectories of these disorders (Anderson et al., 2013, Benros et al., 2014, Berk et al., 2011, Watanabe et al., 2010). The gut is the largest immune system in the body. Microbiota colonization of the gut early in life is crucial for the optimal development and function of the immune

Conflict of interest

The authors have declared that there are no conflicts of interest in relation to the subject of this study.

Funding

This work was supported by National Institute of Mental Health (grant numbers 2R01 MH094151-06 and 5T32 MH019934-24 to DVJ), the Desert-Pacific Mental Illness Research, Education, and Clinical Center (TTN, LTE), the Department of Veterans Affairs Office of Academic Affiliations (TTN), UC San Diego Stein Institute for Research on Aging, and UC San Diego Center for Microbiome Innovation.

References (115)

  • F. Dickerson et al.

    C-reactive protein is associated with the severity of cognitive impairment but not of psychiatric symptoms in individuals with schizophrenia

    Schizophr. Res.

    (2007)
  • B.A. Duerkop et al.

    Immune responses to the microbiota at the intestinal mucosal surface

    Immunity

    (2009)
  • S.J. Evans et al.

    The gut microbiome composition associates with bipolar disorder and illness severity

    J. Psychiatr. Res.

    (2017)
  • J. Flatow et al.

    Meta-analysis of oxidative stress in schizophrenia

    Biol. Psychiatr.

    (2013)
  • T. Frodl et al.

    Is there an association between peripheral immune markers and structural/functional neuroimaging findings?

    Prog. Neuro Psychopharmacol. Biol. Psychiatr.

    (2014)
  • J.K. Goodrich et al.

    Conducting a microbiome study

    Cell

    (2014)
  • C.H. Hennekens et al.

    Schizophrenia and increased risks of cardiovascular disease

    Am. Heart J.

    (2005)
  • E.Y. Hsiao et al.

    Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders

    Cell

    (2013)
  • H. Jiang et al.

    Altered fecal microbiota composition in patients with major depressive disorder

    Brain Behav. Immun.

    (2015)
  • W.J. Katon

    Clinical and health services relationships between major depression, depressive symptoms, and general medical illness

    Biol. Psychiatr.

    (2003)
  • J.R. Kelly et al.

    Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat

    J. Psychiatr. Res.

    (2016)
  • A.D. Kostic et al.

    The microbiome in inflammatory bowel disease: current status and the future ahead

    Gastroenterology

    (2014)
  • S. Leucht et al.

    Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis

    Lancet

    (2009)
  • P. Lin et al.

    Prevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorder

    J. Affect. Disord.

    (2017)
  • K.H. Nuechterlein et al.

    Identification of separable cognitive factors in schizophrenia

    Schizophr. Res.

    (2004)
  • A. Pedersen et al.

    Memory impairment correlates with increased S100B serum concentrations in patients with chronic schizophrenia

    Prog. Neuro Psychopharmacol. Biol. Psychiatr.

    (2008)
  • E.J. Schiffrin et al.

    Immune modulation of blood leukocytes in humans by lactic acid bacteria: criteria for strain selection

    Am. J. Clin. Nutr.

    (1997)
  • E.G. Severance et al.

    Gastrointestinal inflammation and associated immune activation in schizophrenia

    Schizophr. Res.

    (2012)
  • E.G. Severance et al.

    Probiotic normalization of Candida albicans in schizophrenia: a randomized, placebo-controlled, longitudinal pilot study

    Brain Behav. Immun.

    (2017)
  • E.G. Severance et al.

    Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia

    Schizophr. Res.

    (2013)
  • J.S. Bajaj et al.

    Linkage of gut microbiome with cognition in hepatic encephalopathy

    Am. J. Physiol. Gastrointest. Liver Physiol.

    (2012)
  • R. Balamurugan et al.

    Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer

    J. Gastroenterol. Hepatol.

    (2008)
  • C.E. Bearden et al.

    The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review

    Bipolar Disord.

    (2001)
  • S. Brown

    Excess mortality of schizophrenia. A meta-analysis

    Br. J. Psychiatr. J. Ment. Sci.

    (1997)
  • K.F. Budden et al.

    Emerging pathogenic links between microbiota and the gut-lung axis

    Nat. Rev. Microbiol.

    (2017)
  • J.G. Caporaso et al.

    Moving pictures of the human microbiome

    Genome Biol.

    (2011)
  • J. Carr et al.

    Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa?

    Expet Rev. Gastroenterol.

    (2016)
  • D.E. Casey et al.

    Excessive mortality and morbidity associated with schizophrenia

  • E. Castro-Nallar et al.

    Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls

    PeerJ

    (2015)
  • G. Clarke et al.

    The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner

    Mol. Psychiatr.

    (2013)
  • E.K. Costello et al.

    Bacterial community variation in human body habitats across space and time

    Science

    (2009)
  • J.F. Cryan et al.

    Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour

    Nat. Rev. Neurosci.

    (2012)
  • J. Debelius et al.

    Tiny microbes, enormous impacts: what matters in gut microbiome studies?

    Genome Biol.

    (2016)
  • R. Diaz Heijtz et al.

    Normal gut microbiota modulates brain development and behavior

    Proc. Natl. Acad. Sci. U.S.A.

    (2011)
  • H.T. Ding et al.

    Gut microbiota and autism: key concepts and findings

    J. Autism Dev. Disord.

    (2017)
  • M.G. Dominguez-Bello et al.

    Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns

    Proc. Natl. Acad. Sci. U.S.A.

    (2010)
  • S.A. Flowers et al.

    Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort

    Pharmacotherapy

    (2017)
  • K. Forslund et al.

    Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

    Nature

    (2015)
  • P. Forsythe et al.

    Immunomodulation by commensal and probiotic bacteria

    Immunol. Invest.

    (2010)
  • C. Franceschi et al.

    Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases

    J. Gerontol. A Biol. Sci. Med. Sci.

    (2014)
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