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  1. Article ; Online: The Microbiome at the Interface of the Exposome and Risk for Psychiatric Disorders.

    Gur, Tamar L / Hsiao, Elaine Y

    Biological psychiatry

    2024  Volume 95, Issue 4, Page(s) 298–299

    MeSH term(s) Humans ; Exposome ; Microbiota ; Mental Disorders
    Language English
    Publishing date 2024-01-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2023.12.001
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  2. Article: Maternal Exposure to Adversity: Impact on the Microbiota-Gut-Brain Axis, Inflammation and Offspring Psychiatric Outcomes.

    Rajasekera, Therese A / Gur, Tamar L

    Modern trends in psychiatry

    2021  Volume 32, Page(s) 26–39

    Abstract: Psychosocial stress, driven by a variety of sources and influences, can be ubiquitous in our modern society. Prolonged exposure to these stressors can have detrimental biological and psychological effects; extant findings in childhood adversity indicate ... ...

    Abstract Psychosocial stress, driven by a variety of sources and influences, can be ubiquitous in our modern society. Prolonged exposure to these stressors can have detrimental biological and psychological effects; extant findings in childhood adversity indicate that the cumulative effects of exposure to childhood adversity increase risk for developmental delays, altered immune responses, and psychopathology later in life. The pathways by which these effects are conferred continue to be studied. Given that pregnancy is a critical period during which susceptibility to lifetime health and illness are programmed, this chapter will focus on the impacts of maternal history of childhood adversity on offspring mental health, including the role of the microbiota-gut-brain axis. One of the most commonly used frameworks of the last several decades for measuring childhood adversity is the Adverse Childhood Experiences (ACEs) psychometric. We provide an overview of the possible mechanisms through which maternal stress, including the cumulative effects of maternal ACEs, may increase susceptibility to disease in offspring. These include altered epigenetic regulation, hypothalamic-pituitary-adrenal axis function and peripheral inflammation, and gut microbial composition. Finally, we conclude with clinical considerations, including possible future therapeutic interventions.
    MeSH term(s) Adverse Childhood Experiences ; Brain/physiology ; Epigenesis, Genetic ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Maternal Exposure ; Mental Disorders/physiopathology ; Mental Disorders/psychology ; Neuroimmunomodulation/physiology ; Psychopathology ; Psychophysiology ; Stress, Psychological/physiopathology ; Stress, Psychological/psychology
    Language English
    Publishing date 2021-05-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2504-0464
    ISSN 2504-0464
    DOI 10.1159/000510415
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  3. Article ; Online: Biological Psychiatry Podcast Series: Support Resources for the COVID-19 Pandemic.

    Gur, Tamar L / Krystal, John H

    Biological psychiatry

    2020  Volume 88, Issue 1, Page(s) 3

    MeSH term(s) Betacoronavirus/isolation & purification ; Biological Psychiatry ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/psychology ; Humans ; Information Dissemination ; Information Services/organization & administration ; International Cooperation ; Mental Disorders/epidemiology ; Mental Disorders/physiopathology ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/psychology ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-05-13
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2020.05.008
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  4. Article ; Online: The Maternal Microbiome as a Map to Understanding the Impact of Prenatal Stress on Offspring Psychiatric Health.

    Kimmel, Mary C / Verosky, Branden / Chen, Helen J / Davis, Olivia / Gur, Tamar L

    Biological psychiatry

    2023  Volume 95, Issue 4, Page(s) 300–309

    Abstract: Stress and psychiatric disorders have been independently associated with disruption of the maternal and offspring microbiome and with increased risk of the offspring developing psychiatric disorders, both in clinical studies and in preclinical studies. ... ...

    Abstract Stress and psychiatric disorders have been independently associated with disruption of the maternal and offspring microbiome and with increased risk of the offspring developing psychiatric disorders, both in clinical studies and in preclinical studies. However, the role of the microbiome in mediating the effect of prenatal stress on offspring behavior is unclear. While preclinical studies have identified several key mechanisms, clinical studies focusing on mechanisms are limited. In this review, we discuss 3 specific mechanisms by which the microbiome could mediate the effects of prenatal stress: 1) altered production of short-chain fatty acids; 2) disruptions in TH17 (T helper 17) cell differentiation, leading to maternal and fetal immune activation; and 3) perturbation of intestinal and microbial tryptophan metabolism and serotonergic signaling. Finally, we review the existing clinical literature focusing on these mechanisms and highlight the need for additional mechanistic clinical research to better understand the role of the microbiome in the context of prenatal stress.
    MeSH term(s) Pregnancy ; Female ; Humans ; Microbiota ; Mental Disorders/etiology ; Prenatal Exposure Delayed Effects
    Language English
    Publishing date 2023-11-30
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2023.11.014
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    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Intrauterine Microbiota: Missing, or the Missing Link?

    Chen, Helen J / Gur, Tamar L

    Trends in neurosciences

    2019  Volume 42, Issue 6, Page(s) 402–413

    Abstract: The intrauterine environment provides a key interface between the mother and the developing fetus during pregnancy, and is a target for investigating mechanisms of fetal programming. Studies have demonstrated an association between prenatal stress and ... ...

    Abstract The intrauterine environment provides a key interface between the mother and the developing fetus during pregnancy, and is a target for investigating mechanisms of fetal programming. Studies have demonstrated an association between prenatal stress and neurodevelopmental disorders. The role of the intrauterine environment in mediating this effect is still being elucidated. In this review, we discuss emerging preclinical and clinical evidence suggesting the existence of microbial communities in utero. We also outline possible mechanisms of bacterial translocation to the intrauterine environment and immune responses to the presence of microbes or microbial components. Lastly, we overview the effects of intrauterine inflammation on neurodevelopment. We hypothesize that maternal gestational stress leads to disruptions in the maternal oral, gut, and vaginal microbiome that may lead to the translocation of bacteria to the intrauterine environment, eliciting an inflammatory response and resulting in deficits in neurodevelopment.
    MeSH term(s) Animals ; Female ; Fetal Development ; Humans ; Microbiota ; Neurodevelopmental Disorders/etiology ; Pregnancy ; Uterus/microbiology
    Language English
    Publishing date 2019-04-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 282488-7
    ISSN 1878-108X ; 0378-5912 ; 0166-2236
    ISSN (online) 1878-108X
    ISSN 0378-5912 ; 0166-2236
    DOI 10.1016/j.tins.2019.03.008
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  7. Article ; Online: Biological Psychiatry Podcast Series

    Gur, Tamar L. / Krystal, John H.

    Biological Psychiatry

    Support Resources for the COVID-19 Pandemic

    2020  Volume 88, Issue 1, Page(s) 3

    Keywords Biological Psychiatry ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2020.05.008
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  8. Article ; Online: Stress and depression-associated shifts in gut microbiota: A pilot study of human pregnancy.

    Rajasekera, Therese A / Galley, Jeffrey D / Mackos, Amy R / Chen, Helen J / Mitchell, Justin G / Kleinman, Joshua J / Cappelucci, Paige / Mashburn-Warren, Lauren / Lauber, Christian L / Bailey, Michael T / Worly, Brett L / Gur, Tamar L

    Brain, behavior, & immunity - health

    2024  Volume 36, Page(s) 100730

    Abstract: Background: Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut ... ...

    Abstract Background: Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut microbiota-brain axis and associated signaling pathways. Previous preclinical work indicates that prenatal stress alters maternal gut microbial composition and impairs offspring development. Importantly, although the fecal and vaginal microenvironments undergo alterations across pregnancy, we lack consensus regarding which shifts are adaptive or maladaptive in the presence of prenatal stress and depression. Clinical studies interrogating these relationships have identified unique taxa but have been limited in study design.
    Methods: We conducted a prospective cohort study of pregnant individuals consisting of repeated administration of psychometrics (Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D)) and collection of fecal and vaginal microbiome samples. Fecal and vaginal microbial community composition across psychometric responses were interrogated using full-length 16S rRNA sequencing followed by α and β-diversity metrics and taxonomic abundance.
    Results: Early pregnancy stress was associated with increased abundance of fecal taxa not previously identified in related studies, and stress from late pregnancy through postpartum was associated with increased abundance of typical vaginal taxa and opportunistic pathogens in the fecal microenvironment. Additionally, in late pregnancy, maternal stress and depression scores were associated with each other and with elevated maternal C-C motif chemokine ligand 2 (CCL2) concentrations. At delivery, concordant with previous literature, umbilical CCL2 concentration was negatively correlated with relative abundance of maternal fecal
    Conclusion: These findings a) underscore previous preclinical and clinical research demonstrating the effects of prenatal stress on maternal microbiome composition, b) suggest distinct biological pathways for the consequences of stress versus depression and c) extend the literature by identifying several taxa which may serve critical roles in mediating this relationship. Thus, further interrogation of the role of specific maternal microbial taxa in relation to psychosocial stress and its sequelae is warranted.
    Language English
    Publishing date 2024-01-26
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3546
    ISSN (online) 2666-3546
    DOI 10.1016/j.bbih.2024.100730
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  9. Article: Discrete role for maternal stress and gut microbes in shaping maternal and offspring immunity.

    Chen, Helen J / Bischoff, Allison / Galley, Jeffrey D / Peck, Lauren / Bailey, Michael T / Gur, Tamar L

    Neurobiology of stress

    2022  Volume 21, Page(s) 100480

    Abstract: Psychosocial stress is prevalent during pregnancy, and is associated with immune dysfunction, both for the mother and the child. The gut microbiome has been implicated as a potential mechanism by which stress during pregnancy can impact both maternal and ...

    Abstract Psychosocial stress is prevalent during pregnancy, and is associated with immune dysfunction, both for the mother and the child. The gut microbiome has been implicated as a potential mechanism by which stress during pregnancy can impact both maternal and offspring immune function; however, the complex interplay between the gut microbiome and the immune system is not well-understood. Here, we leverage a model of antimicrobial-mediated gut microbiome reduction, in combination with a well-established model of maternal restraint stress, to investigate the independent effects of and interaction between maternal stress and the gut microbiome in shaping maternal and offspring immunity. First, we confirmed that the antimicrobial treatment reduced maternal gut bacterial load and altered fecal alpha and beta diversity, with a reduction in commensal microbes and an increase in the relative abundance of rare taxa. Prenatal stress also disrupted the gut microbiome, according to measures of both alpha and beta diversity. Furthermore, prenatal stress and antimicrobials independently induced systemic and gastrointestinal immune suppression in the dam with a concomitant increase in circulating corticosterone. While stress increased neutrophils in the maternal circulation, lymphoid cells and monocytes were not impacted by either stress or antimicrobial treatment. Although the fetal immune compartment was largely spared, stress increased circulating neutrophils and CD8 T cells, and antibiotics increased neutrophils and reduced T cells in the adult offspring. Altogether, these data indicate similar, but discrete, roles for maternal stress and gut microbes in influencing maternal and offspring immune function.
    Language English
    Publishing date 2022-09-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2816500-7
    ISSN 2352-2895
    ISSN 2352-2895
    DOI 10.1016/j.ynstr.2022.100480
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  10. Article ; Online: Prenatal stress-induced disruptions in microbial and host tryptophan metabolism and transport.

    Galley, Jeffrey D / Chen, Helen J / Antonson, Adrienne M / Gur, Tamar L

    Behavioural brain research

    2021  Volume 414, Page(s) 113471

    Abstract: The aromatic amino acid tryptophan (Trp) is a precursor for multiple metabolites that can steer proper immune and neurodevelopment as well as social behavior in later life. Dysregulation in the Trp metabolic pathways and abundance of Trp or its ... ...

    Abstract The aromatic amino acid tryptophan (Trp) is a precursor for multiple metabolites that can steer proper immune and neurodevelopment as well as social behavior in later life. Dysregulation in the Trp metabolic pathways and abundance of Trp or its derivatives, including indoles, kynurenine (Kyn), and particularly serotonin, has been associated with behavioral deficits and neuropsychiatric disorders including autism spectrum disorders (ASD) and schizophrenia. Previously, we have shown that prenatal stress (PNS) alters placental Trp and serotonin, and reduces Trp-metabolizing members of the maternal colonic microbiota. Given that PNS also results in alterations in offspring neurodevelopment, behavior and immune function, we hypothesized that PNS affects Trp metabolism and transport in both the maternal and fetal compartments, and that these alterations continue into adolescence. We surmised that this is due to reductions in Trp-metabolizing microbes that would otherwise reduce the Trp pool under normal metabolic conditions. To test this, pregnant mice were exposed to a restraint stressor and gene expression of enzymes involved in Trp and serotonin metabolism were measured. Specifically, tryptophan 2,3-dioxygenase, aryl hydrocarbon receptor, and solute carrier proteins, were altered due to PNS both prenatally and postnatally. Additionally, Parasutterella and Bifidobacterium, which metabolize Trp in the gut, were reduced in both the dam and the offspring. Together, the reductions of Trp-associated microbes and concomitant dysregulation in Trp metabolic machinery in dam and offspring suggest that PNS-induced Trp metabolic dysfunction may mediate aberrant fetal neurodevelopment.
    MeSH term(s) Age Factors ; Animals ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Pregnancy ; Prenatal Exposure Delayed Effects/metabolism ; Prenatal Exposure Delayed Effects/microbiology ; Stress, Psychological/metabolism ; Stress, Psychological/microbiology ; Tryptophan/metabolism
    Chemical Substances Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2021-07-16
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2021.113471
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