title: Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring.
abstract: Recent studies demonstrate that exposure to stress changes the composition of the intestinal microbiota, which is associated with development of stress-induced changes to social behavior, anxiety, and depression. Stress during pregnancy has also been related to the emergence of these disorders; whether commensal microbes are part of a maternal intrauterine environment during prenatal stress is not known. Here, we demonstrate that microbiome changes are manifested in the mother, and also found in female offspring in adulthood, with a correlation between stressed mothers and female offspring. Alterations in the microbiome have been shown to alter immune responses, thus we examined cytokines in utero. IL-1β was increased in placenta and fetal brain from offspring exposed to the prenatal stressor. Because IL-1β has been shown to prevent induction of brain derived neurotrophic factor (BDNF), we examined BDNF and found a reduction in female placenta and adult amygdala, suggesting in utero impact on neurodevelopment extending into adulthood. Furthermore, gastrointestinal microbial communities were different in adult females born from stressed vs. non-stressed pregnancies. Adult female offspring also demonstrated increased anxiety-like behavior and alterations in cognition, suggesting a critical window where stress is able to influence the microbiome and the intrauterine environment in a deleterious manner with lasting behavioral consequences. The microbiome may be a key link between the intrauterine environment and adult behavioral changes.
authors.affiliation: Department of Psychiatry & Behavioral Health, Wexner Medical Center at The Ohio State University, United States; Department of Neuroscience, Wexner Medical Center at The Ohio State University, United States; Department of Obstetrics & Gynecology, Wexner Medical Center at The Ohio State University, United States; Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, United States. Electronic address: tamar.gur@osumc.edu.
authors.forename: Tamar L
authors.initials: TL
authors.lastname: Gur
authors.affiliation: Department of Psychiatry & Behavioral Health, Wexner Medical Center at The Ohio State University, United States.
authors.forename: Lena
authors.initials: L
authors.lastname: Shay
authors.affiliation: Department of Psychiatry & Behavioral Health, Wexner Medical Center at The Ohio State University, United States; Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, United States.
authors.forename: Aditi Vadodkar
authors.initials: AV
authors.lastname: Palkar
authors.affiliation: Department of Psychiatry & Behavioral Health, Wexner Medical Center at The Ohio State University, United States; Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, United States; Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, The Ohio State University, United States.
authors.forename: Sydney
authors.initials: S
authors.lastname: Fisher
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, The Ohio State University, United States; Biosciences Division, College of Dentistry, The Ohio State University, United States; Department of Pediatrics, Wexner Medical Center at The Ohio State University, United States.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Varaljay
authors.affiliation: Research and Testing Laboratory and Medical Biofilm Research Institute, Lubbock, TX 79407, United States.
authors.forename: Scot
authors.initials: S
authors.lastname: Dowd
authors.affiliation: Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, United States; Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, The Ohio State University, United States; Biosciences Division, College of Dentistry, The Ohio State University, United States; Department of Pediatrics, Wexner Medical Center at The Ohio State University, United States.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001007:Anxiety; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000378:metabolism / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D010920:Placenta / Q000378:metabolism / Q000382:microbiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000382:microbiology; D011297:Prenatal Exposure Delayed Effects / Q000382:microbiology*; D013315:Stress, Psychological / Q000382:microbiology*; D013559:Symbiosis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; C587672:IL1B protein, mouse; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D009414:Nerve Growth Factors
keywords: Anxiety-like behavior; Gut–brain axis; Microbiota; Placenta; Prenatal stress