Microbiome and Brain Development: A Tale of Two Systems.

BACKGROUND: For the past 2 decades, there has been a growing appreciation of the role that the microbiota (the trillions of microorganisms within and on our bodies) plays as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis across the lifespan but especially during neurodevelopment.

SUMMARY: The gut microbiota and its relevant metabolites interact with the immune and the central nervous systems during critical temporal windows of development. These critical developmental windows perinatally (during the first 1,000 days) are susceptible timepoints for insults that can endure long-lasting effects on the microbiota-gut-brain axis. Accumulating evidence shows that a variety of factors can impact the microbiota in early life, including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress, as well as host genetics. Additionally, sex differences occur in response to microbial manipulations in early life although the underlying mechanisms underpinning such effects remain elusive. Animal models have been essential in delineating the role of the microbiome in neurodevelopmental disorders ranging from autism spectrum disorder to attention deficit hyperactivity disorder. This mechanistic perspective should be supplemented with more translational studies to evaluate the applicability of findings from animal models to human subjects.