The microbiome-gut-brain axis: A new window to view the impact of prenatal stress on early neurodevelopment

Prenatal maternal stress that results from general and pregnancy-specific forms of anxiety and depression, ranging in severity from everyday hassles to experiences of traumatic events, adversely impacts neurodevelopment and increases risks for psychopathology in the offspring. To date, the focus of investigations has been on the assessment of factors that alter fetal brain development via transplacental mechanisms. Attention has to date focused on developmental outcomes associated with transplacental transfer of maternal cortisol and psychotropic medications used to treat stress-related disorders; however, behavioral outcomes across childhood vary and findings remain conflicting and even contradictory. Emerging attention is now focusing on the role of the gastrointestinal microbiome as a key extra-placental stress transfer mechanism during pregnancy. In this chapter, we evaluate empirical evidence for the role of the microbiome-gut-brain axis in a non-transplacental prenatal stress mechanism and links with early brain development. We explore, in both human and animal studies, potential sensitivities for several mechanisms noted to mediate the stress stimuli's neurodevelopmental effects, including hypothalamic-pituitary-adrenal (HPA) axis activity; altered serotonin signaling; changes in placental function; and immune system dysregulation. Special attention is paid to emerging evidence that the gut microbiome may play a consolidating role in shaping these key stress-responsive systems. It is well established that the gut microbiome utilizes neuroendocrine, neuroimmune, and autonomic nervous system pathways to mediate changes in brain function and behavior. Disturbances in the composition of gut microorganisms are a hallmark feature of many neurodevelopmental disorders and such disturbances in the gestational microbiome associated with prenatal stress that can be transferred from mothers to her offspring has been documented, which raised novel questions about whether these changes are associated with early brain development. Fresh approaches are called for refocus on tracking molecular and microbial markers reflective of the underlying etiologies throughout gestation toward identifying biological signatures that correspond to critical periods of vulnerability. Moving forward, targeted manipulation of the gut microbiome via dietary and bacterial-based interventions may prove decisive in conferring resilience to the detrimental consequences of prenatal stress during these critical neurodevelopmental windows.