The importance of appropriate initial bacterial colonization of the intestine in newborn, child, and adult health

Abstract

The fetus does not reside in a sterile intrauterine environment and is exposed to commensal bacteria from the maternal gut/blood stream that cross the placenta and enter the amniotic fluid. This intestinal exposure to colonizing bacteria continues at birth and during the first year of life and has a profound influence on lifelong health. Why is this important? Intestinal crosstalk with colonizing bacteria in the developing intestine affects the infant's adaptation to extrauterine life (immune homeostasis) and provides protection against disease expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing intestinal bacteria are critical to the normal development of host defense. Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section delivery, use of perinatal antibiotics, or premature delivery may adversely affect the gut development of host defense and predispose to inflammation rather than to homeostasis, leading to increased susceptibility to disease later in life. Babies born by cesarean section have a higher incidence of allergy, type 1 diabetes, and obesity. Infants given repeated antibiotic regimens during the first year of life are more likely to have asthma as adolescents. This research breakthrough helps to explain the shift in disease paradigms from infections to immune-mediated in children from developed countries. This review will develop this research breakthrough.

Figure 1

The intestinal epithelial-cell barrier. Simple columnar epithelial cells exhibit physical and biochemical adaptations to microbial colonization to maintain barrier integrity including actin-rich microvillar extensions (a), epithelial-cell tight junctions (b), apically attached and secreted mucins that form a glycocalyx (c) and the production of various anti microbial peptides (d). Specialized intestinal epithelial cells known as M (microfold) cells overlie Peyer’s patches and lymphoid follicles to facilitate luminal sampling. M cells exhibit reduced mucin secretion and have modified apical and basolateral surfaces (e) to promote uptake and transport of luminal contents to professional antigen-presenting cells that inhabit the subepithelial dome (SED) of the Peyer’s patches and lymphoid follicles (f). Specialized dendritic cell (CD) subsets can also extend dendrites between the tight junctions of intestinal epithelial cells to sample luminal contents (g). (Reproduced with permission from reference 16.)

Figure 2

Bacterial metabolites fight intestinal inflammation. Commensal bacteria metabolize fiber and generate short-chain fatty acids. These fatty acids are ligand for GPR43 expressed by T_reg cells and stimulate their expansion and immune-suppressive properties such as the production of IL-10, thereby controlling proinflammatory responses in the gut. (Reproduced from reference 29.)