The Maternal Microbiome as a Map to Understanding the Impact of Prenatal Stress on Offspring Psychiatric Health

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.