Maternal stress during the third trimester of pregnancy and the neonatal microbiome

Abstract

Objectives

Preliminary research suggests that maternal prenatal stress may alter the development of the fetal microbiome and resulting microbial composition after birth. However, the findings of existing studies are mixed and inconclusive. The purpose of this exploratory study was to assess whether maternal stress during pregnancy is associated with the overall number and diversity of various microbial species in the infant gut microbiome or the abundance of specific bacterial taxa.

Methods

Fifty-one women were recruited during their third trimester of pregnancy. The women completed a demographic questionnaire and Cohen’s Perceived Stress Scale at recruitment. A stool sample was collected from their neonate at one month of age. Data on potential confounders, such as gestational age and mode of delivery, were extracted from medical records to control for their effects. 16s rRNA gene sequencing was used to identify the diversity and abundance of microbial species, along with multiple linear regression models to examine the effects of prenatal stress on microbial diversity. We employed negative binomial generalized linear models to test for differential expression of various microbial taxa among infants exposed to prenatal stress and those not exposed to prenatal stress.

Results

More severe symptoms of prenatal stress were associated with a greater diversity of microbial species in the gut microbiome of neonates (β = .30, p = .025). Certain microbial taxa, such as Lactobacillus and Bifidobacterium, were enriched among infants exposed to greater maternal stress in utero, while others, such as Bacteroides and Enterobacteriaceae, were depleted in contrast to infants exposed to less stress.

Conclusions

Findings suggest that mild to moderate stress exposure in utero could be associated with a microbial environment in early life that is more optimally prepared to thrive in a stressful postnatal environment. Adaptation of gut microbiota under conditions of stress may involve upregulation of bacterial species, including certain protective microorganisms (e.g. Bifidobacterium), as well as downregulation of potential pathogens (e.g. Bacteroides) via epigenetic or other processes within the fetal/neonatal gut-brain axis. However, further research is needed to understand the trajectory of microbial diversity and composition as infant development proceeds and the ways in which both the structure and function of the neonatal microbiome may mediate the relationship between prenatal stress and health outcomes over time. These studies may eventually yield microbial markers and gene pathways that are biosignatures of risk or resilience and inform targets for probiotics or other therapies in utero or during the postnatal period.

Keywords:

• Microbiome
• maternal stress
• neonate
• pregnancy
• fetal exposure

Acknowledgments

Dr. Hamidi was supported by a postdoctoral fellowship in the T32 Biobehavioral Research Training Program in Symptom Science (T32 NR016920) funded by the National Institute of Nursing Research and by the Robert C. and Delphine Wentland Eschbach Endowment. We are grateful to Sandra Niemann, PhD; Nina Ahlers, MPH; and Cherry Leung, PhD for their contributions to data collection and data management. We are also grateful to Kei Fujimura, PhD, for her contributions to rRNA sequencing and bioinformatics analysis of RNA-Seq data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author [SJW] upon reasonable request.

Additional information

Funding

This research was funded by NINR (T32 NR016920), NICHD, RO1 HD081188 − 05 (Sandra J. Weiss, Principal Investigator) and the Robert and Delphine Wentland Eschbach Endowment.