Pediatria

Symposium: Bioactivity in Milk and Bacterial Interactions in the Developing Immature Intestine

Modulation of the Gastrointestinal Tract of Infants by Human Milk. Interfaces and Interactions. An Evolutionary Perspective1
Armond S. Goldman
Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, Children’s Hospital, The University of Texas Medical Branch, Galveston, TX77555-0369
ABSTRACT 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 certaininflammatory/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 tractas follows: 1) 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. J. Nutr. 130: 426S– 431S, 2000. KEY WORDS:
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The notion that human milk supplies only nutrients to the infant was still in vogue four decades ago, although there was experimental and clinical evidence to the contrary that dated back to the late 19th century (Goldman 1999). During the last 30 – 40 years, that misconception has been rectified by thefollowing discoveries: 1) a wide spectrum of bioactive agents in human milk (Goldman et al. 1996 and 1997, Koldovsky and Goldman 1999); 2) potential targets in the gastrointestinal (GI)2 tract for those agents; 3) modifications of some functions of the GI tract by breast-feeding; and 4) profound effects upon the function and integrity of the GI by agents from human milk in experimental animals. Someprincipal studies in each
1 Presented at the symposium entitled “Bioactivity in Milk and Bacterial Interactions in the Developing Immature Intestine” as part of the Experimental Biology 99 meeting held April 17–21 in Washington, DC. This symposium was sponsored by the American Society for Nutritional Sciences and the International Society for Research in Human Milk and Lactation and was supportedin part by educational grants from Ross Products Division, Abbott Laboratories and WyethAyerst Laboratories. The proceedings of this symposium are published as a supplement to The Journal of Nutrition. Guest editors for this supplement publication were Richard J. Schanler, Baylor College of Medicine, Houston, TX and Linda C. Duffy, Children’s Hospital of Buffalo, SUNY, Buffalo, NY. 2...