Connection between gut microbiome and brain development in preterm infants

Abstract

Dysbiosis of the gut microbiome in preterm infants predisposes the neonate to various major morbidities including neonatal necrotizing enterocolitis and sepsis in the neonatal intensive care unit, and adverse neurological outcomes later in life. There are parallel early developmental windows for the gut microbiota and the nervous system during prenatal to postnatal of life. Therefore, preterm infants represent a unique population in which optimization of initial colonization and microbiota development can affect brain development and enhance neurological outcomes. In this review, we will first discuss the factors affecting the assembly of neonatal gut microbiota and the contribution of dysbiosis in preterm infants to neuroinflammation and neurodevelopmental disorders. We then will discuss the emerging pathways connecting the gut microbiome and brain development. Further we will discuss the significance of current models for alteration of the gut microbiome (including humanized gnotobiotic models and exposure to antibiotics) to brain development and functions. Understanding the role of early optimization of the microbiome in brain development is of paramount importance for developing microbiome-targeted therapies and protecting infants from prematurity-related neurodevelopmental diseases.

Keywords: brain; microbiome; neurodevelopment; preterm.

Figure 1.

Potential mechanistic pathways by which the gut microbiome may influence maturation of the preterm infant brain. Potential communication/connections between gut microbiota and brain that might have implications in preterm infant brain development include immune system modulation, neurotransmitters and/or neuromodulators produced by gut microbiota, alteration of systemic inflammation and neuroinflammation, signaling between CNS and vagus nerve, and regulation intestinal and blood-brain barrier functions.