Perinatology: Introducing Baby to the Right Bacteria Nutrition: Macrophage Protein May Block Atherosclerosis Medicine: Breathing New Life into Asthma Therapy Genetics: Gene Found for Rare Bone Disorder Leadership: Lipsitz Named the Head of Division on Aging Minority Health: Symposium Seeks to Advance Multicultural Medicine Recognition: HMS and HSPH Professors Win GM Cancer Award New Books: Summer Bookshelf Medical Education: Shore to Lead Promotion and Review Board Dopamine Shown to Inhibit Growth Factor, Block Angiogenesis Embryo Research: To Ease Suffering or Do Nothing? Novel Structural Protein Discovered in Heart and Muscle On Road to Healthy Aging, Each Person Shares Controls Society of General Internal Medicine Presents HMS Professor with Glaser Award Mount Auburn Cited Among Nation's Top Hospitals for Intensive Care Braunwald to Receive Award at World Congress for Heart Research HMS Faculty Teaching Awards Honors and Advances Meeting Aims to Stir Up Solutions for Postdocs The Sacred Trust Beyond Patient and Doctor Call for Writers Front Page

PERINATOLOGY Introducing Baby to the Right Bacteria Breast Milk Could Cut Cases of Deadly GI Inflammation in Premature Infants Parents may idealize their newborn baby as pure and inviolate, but for hundreds of species of microorganism that little bundle of joy is prime real estate. During and after birth, an extensive colonization of this previously pristine territory takes place. And though many people think of foreign invaders only as pathogens, there are more bacteria in our intestines than cells in our body, and most of these tenants do more good than harm. Breast milk and developmental factors help babies stomach good bacteria, according to research by Allan Walker and his lab. Shown clockwise from top: Nanda Nanthakumar, Walker, Kristin Spellmeyer, Robert Fusunyan, Erika Claud, and Lei Lu. Photo by Steve Gilbert In fact, developing a symbiotic relationship with the right bacteria is essential for a baby's health and development. W. Allan Walker, the Conrad Taff professor of nutrition at HMS and Massachusetts General Hospital, has been leading research into the complex relationship among the newborn gastrointestinal system, its bacterial immigrants, and the way breast milk helps regulate the process. In a hypothesis outlined in the June FASEB Journal, Walker and his colleagues propose that the intestines of premature babies are unprepared for an interaction with the external environment, and the resulting mishaps may be the cause of one of the most serious diseases in premature infants, necrotizing enterocolitis. A sometimes fatal gastrointestinal disorder, necrotizing enterocolitis is characterized by intestinal damage and dysfunction. Because it has many risk factors, its cause has been elusive. Various theories have been advanced, including a specific pathogen or intestinal shock. Walker and Erika Claud, HMS instructor in pediatrics at Children's Hospital, have drawn upon their basic research and that of others to suggest that inappropriate colonization of the intestine, in combination with the other risk factors of prematurity and enteral feeding of the newborn, are the key determinants of the disease. Immune Imbalance "Many people think of newborns as not being able to mount an adequate immune response," said Walker. According to this logic, their fragile immune systems make them susceptible to infection. Although this is true in some ways—newborns, for instance, have low levels of IgA antibodies—Walker's lab has shown that fetal cells can be too aggressive in their responses. "Not only are they poor reactors to infectious stimulus, but they in some ways overreact, and that creates problems with disease," Walker said. When exposed to pathogenic bacteria, fetal intestinal cells can produce higher levels of the inflammatory cytokine IL-8 than cells of older children. Examination of tissue from patients with necrotizing enterocolitis also shows elevated levels of inflammatory molecules like platelet-activating factor and lower levels of the enzyme responsible for degrading it. "Our explanation is that babies weren't meant to be born at 26 weeks; they have 14 more weeks to mature," Walker said. "They're coming from an environment where this might be an appropriate reaction to an environment where it causes an inappropriate response." Not only is the immune response of fetal tissue different from that of a full-term newborn, but other developmentally regulated differences cause problems when the fetus is brought prematurely into the outside world. Cells of the intestine have carbohydrate receptors called glycoconjugates at their surface that act as ports for bacteria to land. The types of glycoconjugates ex-pressed can determine the demographics of the populating bacteria, whether good bacteria will thrive or whether the pathologic ones will be able to set up camp. Walker's lab has found evidence that these molecules are developmentally regulated and that the intestines of premature babies have more molecules that are easy targets for harmful bacteria. "These babies aren't supposed to be seeing bacteria," said Walker. The molecules that may function well in a protective bath of amniotic fluid actually make it easier for bad bacteria to attach if the baby is born too early. Breast Milk Therapy Babies do have a natural source of aid in making a transition between such radically different environments. "Nursing is like an extension of the umbilical cord," Walker said. Not only does breast milk provide nutrition, but research is uncovering more and more factors in it that speed the development process. Breast milk contains hormones and growth factors that help the intestines mature and factors that boost the immune system, as well as specific antibodies to pathogens in the mother's—and hence the baby's—environment. But it also contains molecules that tone down inflammation, perhaps preparing the baby to accept nonpathogenic invaders. And it contains sugars that act as receptor decoys for pathogenic bacteria, preventing them from binding to the intestinal wall. Because breast milk seems to play an active role in coaxing the development of the newborn, Walker thinks hospitals should be more adamant in encouraging mothers to provide breast milk to premature babies in intensive care. "They can't nurse properly, but their mothers can express milk and feed it to the baby," he said. And the ultimate aim of this research is to identify factors that can be given to a baby to supplement breast milk or as a substitute when breast milk is not available. Hyaline membrane disease, a condition in which air exchange is hindered in the premature lung, once surpassed necrotizing enterocolitis as the primary emergency in premature babies. The discovery of the chemical that the lungs of premature infants lack, surfactant, has made it possible to treat the disease by infusing artificial surfactant into their lungs. In the case of necrotizing enteroco-litis, factors such as inflammation inhibitors or even beneficial bacteria could be fed to newborns to help their development. —Courtney Humphries A Live Intestinal Tissue Test Figure adapted by Jeff Cleary from original courtesy B. C. Decker, Hamilton. Allan Walker, the Conrad Taff professor of nutrition at HMS and Massachusetts General Hospital, has worked with several colleagues to devise ways of studying the tissue of the fetal and premature intestine. Fetal tissue can legally be obtained only up to 20 weeks into development, short of the age of viable premature babies. Walker and Tor Savidge, HMS assistant professor of pediatrics at MGH, have recently been able to use intestinal tissue obtained from therapeutically aborted fetuses and implant a loop of it under the skin of a mouse lacking immune function. "It develops under the capsule of the mouse just like that same intestine would if it stayed in the womb through gestation," said Walker. "We want to know how well a premature baby can deal with a contaminated external environment. So by looking at these loops we have a simulated situation for a 26- to 30-week-old infant."