New Insights Into Microbiota Modulation-Based Nutritional Interventions for Neurodevelopmental Outcomes in Preterm Infants

Abstract

Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.

Keywords: breast-feeding; infant formula; maternal nutrition in pregnancy; microbiota; preterm.

FIGURE 1

Mean concentration (±SD) of protein (Bauer and Gerss, 2011), IgA (Castellote et al., 2011), lactoferrin (Mastromarino et al., 2014), EGF (Castellote et al., 2011), lysozyme (Hsu et al., 2014), and nine prevalent forms of HMOs (Austin et al., 2019) in the colostrum (<7 days of lactation) and mature milk (1 month of lactation) of mothers that gave birth to extremely preterm (below 29 weeks of gestation), severely preterm (28–32 weeks, excepted for lactoferrin 26–36 weeks), moderately preterm (30–37 weeks) or full term (36–42 weeks) babies. nd, not determined.

FIGURE 2

Key bacterial and fungal colonization of the term and preterm infant gut microbiota from birth through 1 year of life. The composition of the gut microbiota in term and preterm infants varies differently from birth before reaching an identical composition at the first year of life. During the first year of life, pro-inflammatory colonizers are more present in preterm infants than in term infants. The developing term infant gut microbiota is initially dominated by Firmicutes, with low levels of Proteobacteria species, following by an increase in Bifidobacterium and Bacteroides within the first 6 months of life. In contrast, preterm infant gut microbiota is quickly dominated by Proteobacteria species within the first week of life, which remain at high levels throughout the first month and thus induce a delayed progression to a Bifidobacterium-dominated community compared to term infants. In the case of a vaginal delivery, early colonizers originate from the mother’s vaginal and fecal microbiota whereas for C-sections, early colonizers belong to the environment of birth and the mother’s skin microbiota. The gut microbiota differences between vaginally and caesarean delivery disappear after the first year of life.