Modulation of the gastrointestinal tract of infants by human milk, interfaces and interactions. An evolutionary perspective

Human milk contains agents that affect the growth, development and functions of the epithelium, immune system or nervous system of the gastrointestinal tract. Some human and animal studies indicate that human milk affects the growth of intestinal villi, the development of intestinal disaccharidases, the permeability of the gastrointestinal tract and resistance to certain inflammatory/immune-mediated diseases. Moreover, one cytokine in human milk, interleukin (IL)-10, protects infant mice genetically deficient in IL-10 against an enterocolitis that resembles necrotizing enterocolitis (NEC) in human premature infants, There are seven overlapping evolutionary strategies regarding the relationships between the functions of the mammary gland and the infant's gastrointestinal tract as follows: I) certain immunologic agents in human milk compensate directly for developmental delays in those same agents in the recipient infant; 2) other agents in human milk do not compensate directly for developmental delays in the production of those same agents, but nevertheless protect the recipient; 3) agents in human milk enhance functions that are poorly expressed in the recipient; 4) agents in human milk change the physiologic state of the intestines from one adapted to intrauterine life to one suited to extrauterine life; 5) some agents in human milk prevent inflammation in the recipient's gastrointestinal tract; 6) survival of human milk agents in the gastrointestinal tract is enhanced because of delayed production of pancreatic proteases and gastric acid by newborn infants, antiproteases and inhibitors of gastric acid production in human milk, inherent resistance of some human milk agents to proteolysis, and protective binding of other factors in human milk; and 7) growth factors in human milk aid in establishing a commensal enteric microflora.