The Maternal Microbiome: How Stress During Pregnancy Impacts Female Offspring in Adulthood

The Maternal Microbiome: How Stress During Pregnancy Impacts Female Offspring in Adulthood 150 150 Tiasha Letostak, PhD

A recent study suggests a critical window of pregnancy where stress is able to influence the microbiome and intrauterine environment, with lasting behavioral consequences.

Previous research has demonstrated that stress during pregnancy changes the composition of the intestinal microbiota and is related to the emergence of behavioral disorders such as anxiety and depression.

A new study shows that microbiome changes are manifested in the mother and also found in female offspring in adulthood, with a correlation between increased maternal stress and increased anxiety-like behavior as well as cognitive alterations in adult female offspring.

“Stress during pregnancy is an adverse prenatal event that can have a negative effect on fetal neurodevelopment, with long-term behavioral impacts,” says Michael Bailey, PhD, principal investigator in the Center for Microbial Pathogenesis in The Research Institute at Nationwide Children’s Hospital and senior author of the study, which was published in the journal Brain, Behavior, and Immunity. “Stress is known to change the inflammatory state of tissues, promote the release of inflammatory mediators and cytokines from these tissues, and alter the microbiome, which has the capacity to influence behavior.”

Relationships between intrauterine growth factors, hormones, and the immune system are constantly changing and essential to the healthy development of offspring, and modifications in the microbiome have been shown to impact these relationships and alter immune responses.

To elucidate whether commensal microbes are part of a maternal intrauterine environment during prenatal stress, Dr. Bailey and his colleagues examined cytokines in utero in both the placenta and the fetal brain of offspring.

“Interleukin-1β was increased in the placenta and fetal brain from offspring whose mothers were exposed to prenatal stress,” says Tamar Gur, MD, PhD, maternal-fetal psychiatrist at The Ohio State University and first author of the study. “Since IL-1β has been shown to prevent induction of brain derived neurotrophic factor, we examined BDNF and found a decrease in the female placenta and adult amygdala, indicating an in utero impact on neurodevelopment that extends into adulthood.”

Dr. Bailey and his team also found that gastrointestinal microbial communities differed between adult females born from stressed versus non-stressed pregnancies, and that adult female offspring exposed to prenatal stress also showed increased anxiety-like behavior and cognitive alterations.

“Our work indicates that the microbiome may be a key link between the intrauterine environment and adult behavioral changes,” says Dr. Bailey, who is also an associate professor of Pediatrics at The Ohio State University. “There is a crucial time frame when stress is able to influence the microbiome and the intrauterine environment in a deleterious manner.”

Dr. Gur notes that they focused on the development of anxiety-like behavior in females because anxiety is more common in women, but they plan to include data from male offspring in future studies of gestational stress.



Gur TL, Shay L, Palkar AV, Fisher S, Varaljay VA, Dowd S, Bailey MT. Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspringBrain, Behavior, and Immunity. 2016 Dec 24. [Epub ahead of print]

About the author

Tiasha is the senior strategist for Clinical & Research Communications at Nationwide Children's Hospital. She provides assistance to investigators in The Research Institute and clinician-scientists at Nationwide Children’s for internal and external communication of clinical studies, peer-reviewed journal articles, grant awards and research news. She is also the editor-in-chief for Research Now, Nationwide Children's monthly, all-employee e-newsletter for research, as well as a writer for Pediatrics Nationwide.