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.

Alpha-Lactalbumin Enriched Whey Protein Concentrate to Improve Gut, Immunity and Brain Development in Preterm Pigs

“…Appropriate milk proteins may diversify the gastrointestinal microbiome, similar to the effects of breast milk [22]. This would help avoid the dysbiosis seen in patients with NEC and/or sepsis [53]. Even though FISH analysis showed a similar bacterial abundance in the distal small intestine of HIGH-ALPHA and STANDARD-ALPHA, the minor increase in the number of different bacterial species in HIGH-ALPHA indicates a slight stimulation of beneficial bacteria with increased dietary α-Lac in the preterm gut.…”

“…There is growing evidence that the bidirectional communication within the microbiota-gut-brain axis is critical for health, cognition, brain and organ development [53,56]. The trajectories of microbiotaoriginated communication with organ systems and the brain might involve their metabolites, such as SCFAs [56].…”

Meconium microbiome and its relation to neonatal growth and head circumference catch-up in preterm infants

“…neurodevelopmental disability, with long term effects [3,40,41]. Catch down during hospital stay and during the first months of life are associated to increased risk of neurologic impairment in preterm infants, nevertheless the mechanisms that guarantee this association are not yet completely elucidated [6].…”

“…Taken together, neurological immaturity and a dysbiotic and immature gut, both associated with prematurity may disrupt the bidirectional communication between the nervous system and enteric cells, leading to altered signaling and neurological development, and also altered immune responses [3,44,45].…”

Gestational-age-dependent development of the neonatal metabolome

“…It is likely that the individual maturation more accurately represents the complication risk. Growing evidence suggests a strong link between early-life microbiota and disease (6) and short-as well as long-term complications associated with preterm birth such as necrotizing enterocolitis, diabetes, cardiovascular disease, neurodevelopmental disorders and neuropsychiatric disorders have been related to the underdevelopment of the gut microbiota, gastrointestinal tract and immune system (7)(8)(9)(10)(11)(12)(13). Although the exact timing of the establishment of the intestinal microbiome in human life remains unknown (14), it is generally agreed upon that the gut microbial colonization starts at birth at the latest and undergoes shifts in composition and structure as the host matures over time (15)(16)(17)(18)(19).…”