Maternal Stress Reprogramming of the Developing Gut Microbiome-Brain Axis
Eldin Jasarevic, University of Pennsylvania
Stress pathway dysregulation is the most pervasive symptom in neuropsychiatric disease, yet we understand little as to the developmental programming and maturation of this system as well as the sensitive periods during adversity may be disruptive. Stress during pregnancy has been strongly associated with an increased incidence neurodevelopmental disorders, including depression, anxiety, schizophrenia, autism. Mechanisms through which maternal stress experience during pregnancy contributes to reprogramming of stress pathways likely involve complex connections between the maternal and fetal environments. One such interaction that our lab is currently exploring is the effect maternal stress on the vaginal microbiome. During parturition, the neonate ingests the primary inoculum of microbes as it passes through the birth canal, the composition of which is becoming recognized to have critical implications on long-term health outcomes. Indeed, these pioneer colonizers are essential for instructing the immune system, maintaining resistance to infection, maturing the intestinal tract, and metabolism. Thus, to examine the hypothesis that alterations in the maternal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we utilized a multidimensional approach that integrates numerous ‘omics platforms in our mouse model of early prenatal stress. In addition, we examined whether aspects of our early prenatal stress phenotype is transferrable by colonizing offspring with stress-altered maternal microbiota. Taken together, these studies highlight a novel role of the maternal microbiome in intergenerational gut-brain communication.