Programming Bugs: Microbiota and the Developmental Origins of Brain Health and Disease

Abstract

It has been nearly 30 years since Dr. David Barker first highlighted the importance of prenatal factors in contributing to the developmental origins of adult disease. This concept was later broadened to include postnatal events. It is clear that the interaction between genetic predisposition and early life environmental exposures is key in this regard. However, recent research has also identified another important factor in the microbiota-the trillions of microorganisms that inhabit key body niches, including the vagina and gastrointestinal tract. Because the composition of these maternal microbiome sites has been linked to maternal metabolism and is also vertically transmitted to offspring, changes in the maternal microbiota are poised to significantly affect the newborn. In fact, several lines of evidence show that the gut microbiota interacts with diet, drugs, and stress both prenatally and postnatally and that these exogenous factors could also affect the dynamic changes in the microbiota composition occurring during pregnancy. Animal models have shown great utility in illuminating how these disruptions result in behavioral and brain morphological phenotypes reminiscent of psychiatric disorders (anxiety, depression, schizophrenia, and autism spectrum disorders). Increasing evidence points to critical interactions among the microbiota, host genetics, and both the prenatal and postnatal environments to temporally program susceptibility to psychiatric disorders later in life. Sex-specific phenotypes may be programmed through the influence of the microbiota on the hypothalamic-pituitary-adrenal axis and neuroimmune system.

Keywords: Brain development; Early life; Gut-brain axis; Microbiota; Neuropsychiatry; Stress.