The role of gut microbiota in programming the immune phenotype

Abstract

The human fetus lives in a germ-free intrauterine environment and enters the outside world containing microorganisms from several sources, resulting in gut colonization. Full-term, vaginally born infants are completely colonized with a diverse array of bacterial families in clusters (Phyla) and species (>1000) by the first year of life. Colonizing bacteria communicating with the gut epithelium and underlying lymphoid tissues (‘bacterial–epithelial crosstalk’) result in a functional immune phenotype and no expression of disease (immune homeostasis). Appropriate colonization is influenced by the prebiotic effect of breast milk oligosaccharides. Adequate colonization results in an innate and adaptive mucosal immune phenotype via communication between molecular patterns on colonizing bacteria and pattern-recognition receptors (e.g., toll-like receptors) on epithelial and lymphoid cells. This ontogeny affects the immune system's capacity to develop oral tolerance to innocuous bacteria and benign antigens. Inadequate intestinal colonization with premature delivery, delivery by Cesarean section and excessive use of perinatal antibiotics results in the absence of adequate bacterial–epithelial crosstalk and an increased incidence of immune-mediated diseases [e.g., asthma, allergy in general and necrotizing enterocolitis (NEC)]. Fortunately, infants with inadequate intestinal colonization can be restored to a bacterial balance with the intake of probiotics. This has been shown to prevent debilitating diseases such as NEC. Thus, understanding the role of gut microbiota in programming of the immune phenotype may be important in preventing disease expression in later childhood and adulthood.

Breast milk, microbiota, and intestinal immune homeostasis

“…Commensal luminal bacteria interacting through pattern recognition receptors can stimulate these dendritic cells to release cytokines, which create a microenvironment that allows naïve T-helper cells (TH0) to create balanced subclasses of TH cells (TH1, TH2, TH17, and THreg) (Figure 3). Newborn infants are born with a TH2 bias to protect them from intrauterine rejection (8,37). It takes appropriate colonization of the newborn to shift this bias to balanced TH cell subsets for effective adaptive immunity.…”

“…These oligosaccharides pass undigested through the small intestine and enter the colon where they are fermented by endogenous microbiota (63). Extensive observations over the last two decades have established the impact of breast milk, particularly oligosaccharides, on the microbial composition of the intestine and its effect on gut development, particularly immune homeostasis (37,62). The term prebiotic has been used to describe the endogenous bacterial stimulatory effect of breast milk oligosaccharides (4).…”

“…Fortuitously, these individual species have been shown to Review have important, unique functions in the developing mucosal immune system as discussed above, which appear to affect the newborn's immune system in the very important postpartum period. Furthermore, this early activation of the mucosal immune system appears to provide lifelong protection against expression of disease (8,18,37).…”

Intestinal Microbiocenosis, Food Tolerance and Food Allergy. Current State of a Problem

“…Колонизация кишечника естественной микрофлорой, совпадающая по времени с началом энтерального посту-пления пищевых антигенов, запускает финальные стадии созревания иммунной системы с преимущественной под-держкой функции T х1 -иммунных реакций для достижения необходимой устойчивости баланса T х1 /T х2 [36,40]. При этом считается, что толерантность к симбионтной микро-флоре формируется с участием тех же механизмов, что и толерантность к пищевым антигенам [36,40,41].…”

“…При этом считается, что толерантность к симбионтной микро-флоре формируется с участием тех же механизмов, что и толерантность к пищевым антигенам [36,40,41].…”