Determinants of microbial colonization in the premature gut

Abstract

Abnormal microbial colonization in the gut at an early stage of life affects growth, development, and health, resulting in short- and long-term adverse effects. Microbial colonization patterns of preterm infants differ from those of full-term infants in that preterm babies and their mothers have more complicated prenatal and postnatal medical conditions. Maternal complications, antibiotic exposure, delivery mode, feeding type, and the use of probiotics may significantly shape the gut microbiota of preterm infants at an early stage of life; however, these influences subside with age. Although some factors and processes are difficult to intervene in or avoid, understanding the potential factors and determinants will help in developing timely strategies for a healthy gut microbiota in preterm infants. This review discusses potential determinants of gut microbial colonization in preterm infants and their underlying mechanisms.

Keywords: Antibiotics; Delivery mode; Dysbiosis; Gut microbiota; Human breast milk; Microbial colonization; Preterm infant; Probiotics.

Fig. 1

Potential strategies for improving dysbiosis in preterm infants (PTIs). The human milk microbiome and human milk oligosaccharides (HMOs) can effectively protect the gut microbiota (GM) in PTIs. Probiotics administration and fecal microbiota transplantation (FMT) can be used to improve preterm intestinal dysbiosis

Fig. 2

Factors shaping the preterm infant (PTI) gut microbiota during early life and evolution During the first weeks after birth, the human infant gut is colonized by facultative anaerobes, such as Enterobacteriaceae, Streptococcus, Enterococcus, and Staphylococcus. PTIs are more highly colonized by Staphylococcus than are full-term infants (FTIs) during this period, and PTIs gradually become dominated by anaerobic genera, including Bifidobacterium, Bacteroides, and Clostridium. Between 10 days and 3 months of age, Enterococcaceae and Lactobacilli dominance is observed in premature babies. After cessation of breastfeeding and the addition of solid foods, the gut microbiota gradually becomes dominated mainly by members of the anaerobic class Clostridia, a process required for maturation into an adult-like microbiota

Fig. 3

Entero-mammary pathway Dendritic cells send dendrites out of the epithelium through tight junctions. Dendritic cells carrying bacteria migrate to the mesenteric lymph nodes, lactate mammary glands, and ultimately into milk. Through this entero-mammary pathway, the maternal gut microbiota (GM) finally reaches the gut of preterm infants (PTIs)

Fig. 4

Human milk oligosaccharides (HMOs) promote the growth of “good bacteria” and inhibit pathogenic colonization HMOs help establish a healthy gut microbiota (GM) in at least two ways. First, HMOs exhibit a probiotic effect, promoting the growth of beneficial bacteria and inhibiting the growth of pathogens. Second, HMOs act as decoy receptors and bind pathogens, competing with them through adhesion to their receptors on epithelial cells, suppressing the colonization of pathogenic bacteria