Gastrointestinal host defence: importance of gut closure in control of macromolecular transport

Abstract

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of harmful substances (bacteria, toxins and antigens) present within the intestinal lumen. At birth, the newborn infant must be prepared to deal with bacterial colonization of the gut, with formation of toxic byproducts of bacteria and viruses (enterotoxins and endotoxins) and with the ingestion of antigens (milk proteins). These potentially noxious substances if allowed to penetrate the mucosal epithelial barrier under pathological conditions can cause inflammatory and allergic reactions which may result in gastrointestinal and systemic disease states. To combat the potential danger of invasion across the mucosal barrier the infant must develop an elaborate system of defence mechanisms within the lumen and on the luminal mucosal surface which act to control and maintain the epithelium as an impermeable barrier to uptake of macromolecular antigens. These defences include a unique immunological system adapted to function in the complicated milieu of the intestine as well as other non-immunological processes such as a gastric barrier, intestinal surface secretions, peristaltic movement and natural antibacterial substances (lysozyme, bile salts) which also help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, particularly for premature and small-for-dates infants, this elaborate local defence system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier newborn infants are particularly vulnerable to pathological penetration by harmful intraluminal substances. The consequences of altered defence are susceptibility to infection and the potential for hypersensitivity reactions and for formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis and hepatitis. Fortunately, 'nature' has provided a means for passively protecting the 'vulnerable' newborn against dangers of a deficient intestinal defence system, namely human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leucocytes but many other substances which can interfere with bacterial colonization and prevent antigen penetration.