Why is initial bacterial colonization of the intestine important to infants' and children's health?

Abstract

Microbial colonization of the infant occurs during a critical time window for immune and gastrointestinal development. Infant colonization sets the stage for the adult microbiome. This review is a broad survey of the factors affecting infant colonization and the downstream effects on gastrointestinal health and disease. Major topics affecting colonization include initial inoculation dependent on birth mode, the impact of breast-feeding, and inside-out modulation of the developing microbiome by the immune system. Major outcomes of colonization include the timing-dependent education of the neonatal immune system, which is interconnected with barrier function and metabolism. These all engage in further continuing cross-talk with the microbiome, genetics, and nutrition. This review also briefly examines mechanisms of disease resulting from disrupted colonization as well as nutritional and microbial therapies.

Figure 1. Symbiotic Bacterial Induction of sIgA Via Dendritic Cells

Dendritic cells sample gut bacteria, which stimulates the formation of local sIgA by plasma cells. This sIgA is distributed along the length of the gut but not systemically. This allows the immune system to block antigenic stimulation at the epithelial surface and preserve systemic reactivity should the bacterium pass the epithelial barrier. Adapted from Hooper et al. Science 2004;303:1662–65.

Figure 2. Early Colonization, Invariant Natural Killer T (iNKT) Cells in the Colon and Disease

(Left) Colonization of germ free (GF) mice during the newborn period (GF/n) is sufficient to program the immune system to prevent iNKT cell accumulation in the colon. When GF mice are colonized as adults (GF/a), their immune system persists with the same phenotype as a GF mouse. (Right) GF mice and GF/a mice are susceptible to ulcerative colitis. GF/n mice are protected from colitis by colonization in infancy. Reproduced with permission from Olszak et al. Science 2012;336:489–493.

Figure 3. Cross-talk between microbiome and intestinal homeostasis

Initial infant colonization results from genetics, microbial exposures such as delivery mode and antibiotic usage, and breast feeding. This, in turn, sets in motion the cross-talk between the microbiome, nutrition, immunity, barrier function, metabolism and gene expression. The initial colonization of the infant and microbiome-directed therapies represent a major avenue for prevention and treatment of immune and metabolic disease.