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Principal Investigator: Tamara Sonia Bodnar
Organization: BROCK UNIVERSITY
Fiscal Year: 2024
Award: $242,144
Funding agency: National Institute on Alcohol Abuse and Alcoholism
7. Project Summary/Abstract
Studies in both animal models and human cohorts have demonstrated broad impacts of prenatal alcohol
exposure (PAE) on immune function. We showed, for the first time that PAE results in a more severe and
prolonged course of inflammation in response to immune challenge in adulthood, which appears to have its
origins in a proinflammatory bias that is present from birth. Inflammation, increased gut permeability, and
changes in gut microbiota composition have been implicated in the pathogenesis of wide range of diseases/
disorders, including depression and anxiety. Notably, approximately 90% of individuals with Fetal Alcohol
Spectrum Disorders (FASD) experience mental health problems at some point in their lives, with depression and
anxiety being the most common. Yet links between immune/inflammatory function and mental health outcomes
are not well studied in the FASD field, and to date there are no publications examining PAE effects on gut
structure, function, and microbiota composition, nor whether such changes may underlie alterations in immune
function. The present proposal will fill these gaps by exploring the complex interplay among PAE-induced
alterations in gut structure, function, and microbiota composition, immune function, and emotional dysregulation
(operationalized here as adverse mental health outcomes). The potential beneficial impact(s) of intervention
strategies including pharmacological treatments and fecal transplant will be explored, and a translational
experiment will investigate possible associations between PAE-induced emotional dysregulation and altered gut
microbiota composition in a human cohort. Our goal is to explore potential novel biomarkers of PAE and inform
future clinical strategies to improve health and well-being of individuals with FASD. Our Specific Aims are to:
1) Determine the effects of PAE on gut structure, function and microbiota composition and how these may affect
immune function and set the stage for risk for/resilience to emotional dysregulation; 2) Investigate the
effectiveness of pharmacological treatments in ameliorating PAE-induced alterations in gut structure, function,
microbiota composition, immune function, and emotional dysregulation; 3) Evaluate the efficacy of fecal
microbiota transplantation in ameliorating PAE-induced alterations in gut structure, function, microbiota
composition, immune function, and emotional dysregulation; and 4) Translate this work to a human cohort by
investigating associations among PAE-induced alterations in gut permeability, microbiota composition, and
emotional dysregulation in adults with FASD. Our working hypothesis is that PAE: impacts structure and
function of the gut barrier, leading to increased permeability to luminal products; causes a shift in gut microbiota
composition and altered signaling in the gut-brain axis; and together, these changes may be key drivers of the
early proinflammatory bias and lifelong perturbations in immune function that ultimately negatively impact mental
health status. This research will provide unique insight into factors underlying PAE-related risk and resilience.
Terms: <0-11 years old><21+ years old><Adult><Adult Human><Affect><Alcohol Chemical Class><Alcohol Drinking><Alcohol consumption><Alcohols><Animal Model><Animal Models and Related Studies><Anxiety><Bacteria><Birth><Blood Circulation><Bloodstream><Brain><Brain Nervous System><Cell Communication and Signaling><Cell Signaling><Cellular Immune Function><Child><Child Youth><Children (0-21)><Chronic><Clinical><Clinical Research><Clinical Study><Clinical Treatment><Complex><Development><Disease><Disorder><Early Intervention><Effectiveness><Encephalon><Environment><EtOH drinking><EtOH use><FASD><Fetal Alcohol Exposure><Fetal Alcohol Spectrum Disorder><Fetal ETOH Exposure><Fetal Ethanol Exposure><Fetal alcohol effects><Future><GI microbiota><Gastrointestinal microbiota><Gestation><Goals><Grant><Gut Epithelial Permeability><Gut Hyperpermeability><Gut permeability><Health><Health Status><Human><Immune><Immune Cell Activation><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immune system><Immunes><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Impairment><In Utero Alcohol Exposure><In Utero ETOH Exposure><In Utero Ethanol Exposure><Incidence><Individual><Infant><Inflammation><Inflammatory><Intervention><Intervention Strategies><Intestinal Epithelial Permeability><Intestinal Hyperpermeability><Intestinal Leakage><Intestinal permeability><Intracellular Communication and Signaling><Leaky Gut><Level of Health><Life><Life Cycle><Life Cycle Stages><Link><Literature><Mental Depression><Mental Health><Mental Hygiene><Mental disorders><Mental health disorders><Modern Man><Neuroendocrine><Neuroendocrine System><Neuroimmune><Neurosecretory Systems><Organism><Outcome><Parturition><Pathogenesis><Pattern><Peripheral><Permeability><Personal Satisfaction><Pharmacological Treatment><Predisposition><Pregnancy><Prenatal Alcohol Exposure><Prenatal ETOH Exposure><Prenatal Ethanol Exposure><Psychiatric Disease><Psychiatric Disorder><Psychological Health><Publications><Recovery><Research><Risk><Scientific Publication><Severities><Signal Transduction><Signal Transduction Systems><Signaling><Structure><Susceptibility><System><Time><Translating><Woman><Work><adulthood><alcohol consumption during pregnancy><alcohol during pregnancy><alcohol ingestion><alcohol intake><alcohol intake during pregnancy><alcohol product use><alcohol use><alcohol-exposed pregnancy><alcoholic beverage consumption><alcoholic drink intake><biological signal transduction><cohort><depression><determine efficacy><developmental><disease risk><disorder risk><drinking alcohol during pregnancy><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><emotion dysregulation><emotional dysregulation><enteric microbial community><enteric microbiota><ethanol consumption><ethanol consumption during pregnancy><ethanol drinking><ethanol ingestion><ethanol intake><ethanol product use><ethanol use><evaluate efficacy><examine efficacy><experience><experiment><experimental research><experimental study><experiments><exposed to alcohol prenatally><fecal microbial transplantation><fecal microbiome transplantation><fecal microbiota transplant><fecal microbiota transplantation><fecal transplant><fecal transplantation><gastrointestinal microbial flora><gestation ETOH exposure><gestation alcohol exposure><gestation ethanol exposure><gestational ethanol exposure><gut commensal><gut community><gut flora><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiota><gut microbiotic><gut microflora><gut to brain axis><gut-brain axis><gut-brain communication><gut-brain interactions><gut-brain relationship><gut-brain signaling><health level><host response><immune activation><immune function><immune system response><immunoresponse><improved><infancy><infantile><insight><interventional strategy><intestinal flora><intestinal microbiota><intestinal microflora><intestinal tract microflora><intra-uterine environment><intrauterine environment><intrauterine milieu><kids><late life><life course><life span><lifespan><living system><mental illness><microbial consortia><microbial flora><microbiota><microbiota composition><microflora><model of animal><multispecies consortia><new marker><novel><novel biomarker><novel marker><pregnancy ETOH exposure><pregnancy alcohol exposure><pregnancy ethanol exposure><prenatal><prenatal alcohol consumption><prenatal alcohol effect><prenatal alcohol use><prenatal drinking><prenatally alcohol exposed><prenatally exposed to alcohol><programs><psychiatric illness><psychological disorder><resilience><resilient><response><treatment strategy><trial regimen><trial treatment><unborn><well-being><wellbeing><youngster>