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Programming Bugs: Microbiota and the Developmental Origins of Brain Health and Disease

  • Author Footnotes
    1 MGC and SS contributed equally to this work.
    Martin G. Codagnone
    Footnotes
    1 MGC and SS contributed equally to this work.
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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  • Author Footnotes
    1 MGC and SS contributed equally to this work.
    Simon Spichak
    Footnotes
    1 MGC and SS contributed equally to this work.
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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  • Siobhain M. O’Mahony
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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  • Olivia F. O’Leary
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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  • Gerard Clarke
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland

    Irish Centre for Fetal and Neonatal Translational Research and Cork University Maternity Hospital, University College Cork, Cork, Ireland
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  • Catherine Stanton
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Irish Centre for Fetal and Neonatal Translational Research and Cork University Maternity Hospital, University College Cork, Cork, Ireland

    Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
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  • Timothy G. Dinan
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
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  • John F. Cryan
    Correspondence
    Address correspondence to John F. Cryan, Ph.D., Professor and Chair, Department of Anatomy and Neuroscience, 386 Western Gateway Building, University College Cork, Cork, Ireland.
    Affiliations
    APC Microbiome Ireland, University College Cork, Cork, Ireland

    Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
    Search for articles by this author
  • Author Footnotes
    1 MGC and SS contributed equally to this work.

      Abstract

      It has been nearly 30 years since Dr. David Barker first highlighted the importance of prenatal factors in contributing to the developmental origins of adult disease. This concept was later broadened to include postnatal events. It is clear that the interaction between genetic predisposition and early life environmental exposures is key in this regard. However, recent research has also identified another important factor in the microbiota—the trillions of microorganisms that inhabit key body niches, including the vagina and gastrointestinal tract. Because the composition of these maternal microbiome sites has been linked to maternal metabolism and is also vertically transmitted to offspring, changes in the maternal microbiota are poised to significantly affect the newborn. In fact, several lines of evidence show that the gut microbiota interacts with diet, drugs, and stress both prenatally and postnatally and that these exogenous factors could also affect the dynamic changes in the microbiota composition occurring during pregnancy. Animal models have shown great utility in illuminating how these disruptions result in behavioral and brain morphological phenotypes reminiscent of psychiatric disorders (anxiety, depression, schizophrenia, and autism spectrum disorders). Increasing evidence points to critical interactions among the microbiota, host genetics, and both the prenatal and postnatal environments to temporally program susceptibility to psychiatric disorders later in life. Sex-specific phenotypes may be programmed through the influence of the microbiota on the hypothalamic-pituitary-adrenal axis and neuroimmune system.

      Keywords

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