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August 03, 2010

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Why is breast milk best? It’s in the genes, scientists say

May 13, 2010
Courtesy of the University of Illinois
and World Science staff

Is breast milk so dif­fer­ent from in­fant for­mu­la? Yes, say sci­en­tists, who in a new study have com­pared breast-fed and for­mu­la-fed ba­bies by tracking which genes are op­er­at­ing in their in­tes­tines.

It turns out that breast milk stim­u­lates “ge­netic path­ways that are quite dif­fer­ent from those in for­mu­la-fed in­fants,” said Uni­vers­ity of Il­li­nois nu­tri­tion­ist Shar­on Dono­van, who with col­leagues con­ducted the stu­dy. “Al­though for­mu­la mak­ers have tried to de­vel­op a prod­uct that’s as much like breast milk as pos­si­ble, hun­dreds of genes were ex­pressed [ac­ti­vat­ed] dif­fer­ently in the breast-fed and for­mu­la-fed groups.”

Al­though both breast-fed and for­mu­la-fed ba­bies gain weight and seem to de­vel­op sim­i­lar­ly, studies have found that breast milk con­tains im­mune-protective com­po­nents that make a breast-fed in­fant’s risk low­er for many ill­nesses. (Image cour­tesy Id­aho Dept. of Health & Wel­fare)
Al­though both breast-fed and for­mu­la-fed ba­bies gain weight and seem to de­vel­op sim­i­lar­ly, sci­en­tists have known for a long time that breast milk con­tains im­mune-protective com­po­nents that make a breast-fed in­fant’s risk low­er for all kinds of ill­nesses, she said.

“The in­tes­ti­nal tract of the new­born un­der­goes marked changes in re­sponse to feed­ing. And the re­sponse to hu­man milk ex­ceeds that of for­mu­la, sug­gest­ing that the bioac­tive com­po­nents in breast milk are im­por­tant in this re­sponse,” she not­ed. “What we haven’t known is how breast milk pro­tects the in­fant and par­tic­u­larly how it reg­u­lates the de­vel­op­ment of the in­tes­tine.”

Un­der­stand­ing those dif­fer­ences should help for­mu­la mak­ers de­vel­op a prod­uct more like the real thing, she said. The sci­en­tists hope to de­vel­op a sig­na­ture gene or group of genes to use as a “biomark­er” for breast-fed in­fants. Many of the dif­fer­ences found by the sci­en­tists were in genes known to reg­u­late the de­vel­op­ment of the in­tes­tine and pro­vide im­mune de­fense.

Dono­van used a new tech­nique patented by Tex­as A&M Uni­vers­ity col­league Rob­ert Chap­kin to ex­am­ine in­tes­ti­nal gene ac­ti­vat­ion in 22 healthy in­fants—12 breast-fed, 10 for­mu­la-fed. The tech­nique in­volved iso­lat­ing in­tes­ti­nal cells shed in the in­fants’ poop. In these cells, chem­i­cal traces of dif­feri­ng gene ac­tiv­ation levels could be found.

Un­der­stand­ing early in­tes­ti­nal de­vel­op­ment is im­por­tant for many rea­sons, Dono­van said. “An in­fant’s gut has to adapt very quick­ly. A new ba­by is com­ing out of a ster­ile en­vi­ron­ment, hav­ing re­ceived all its nu­tri­ents in­tra­ve­nously through the pla­cen­ta. At that point, ba­bies ob­vi­ously must beg­in eat­ing, ei­ther moth­er’s milk or for­mu­la.

“They al­so start to be­come col­o­nized with bac­te­ria, so it’s very im­por­tant that the gut learns what’s good and what’s bad. The ba­by’s body needs to be able to rec­og­nize a bad bac­te­ria or a bad vi­rus and fight it, but it al­so needs to rec­og­nize that even though a food pro­tein is for­eign, that pro­tein is okay and the body does­n’t want to de­vel­op an im­mune re­sponse to it,” she said.

If an­y­thing goes wrong at this stage, ba­bies can de­vel­op food al­ler­gies, in­flam­ma­to­ry bow­el dis­ease, and even asth­ma. “We’re very in­ter­est­ed in fre­quent sam­pling at this early pe­ri­od of de­vel­op­ment,” she added.

Dono­van al­so wants learn how bac­te­ria in the gut dif­fer in for­mu­la- and breast-fed ba­bies. “Now we’ll be able to get a com­plete pic­ture of what’s hap­pen­ing in an in­fant—from the com­po­si­tion of the di­et to the mi­crobes in the gut and the genes that are ac­ti­vat­ed along the way.”

Of po­ten­tial clin­i­cal im­por­tance: the gene ex­pressed most of­ten in breast-fed in­fants is in­volved in the cel­l’s re­sponse to ox­y­gen de­priva­t­ion. Lack of ox­y­gen is a fac­tor in the de­vel­op­ment of nec­ro­tiz­ing en­ter­o­co­litis, a kind of gan­grene of the in­tes­tine that can be fa­tal in prem­a­ture ba­bies and is a lead­ing cause of dis­ease and death in ne­o­na­tal in­ten­sive care un­its.

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Is breast milk so different from infant formula? The ability to track which genes are operating in an infant’s intestine has allowed scientists to compare the early development of breast-fed and formula-fed babies. They say the difference is very real. It turns out that breast milk stimulates “genetic pathways that are quite different from those in formula-fed infants. Although formula makers have tried to develop a product that’s as much like breast milk as possible, hundreds of genes were expressed [activated] differently in the breast-fed and formula-fed groups,” said University of Illinois nutritionist Sharon Donovan. Although both breast-fed and formula-fed babies gain weight and seem to develop similarly, scientists have known for a long time that breast milk contains immune-protective components that make a breast-fed infant’s risk lower for all kinds of illnesses, she said. “The intestinal tract of the newborn undergoes marked changes in response to feeding. And the response to human milk exceeds that of formula, suggesting that the bioactive components in breast milk are important in this response,” she noted. “What we haven’t known is how breast milk protects the infant and particularly how it regulates the development of the intestine.” Understanding those differences should help formula makers develop a product more like the real thing, she said. The scientists hope to develop a signature gene or group of genes to use as a “biomarker” for breast-fed infants. Many of the differences found by the scientists were in genes known to regulate the development of the intestine and provide immune defense for the infant. Donovan used a new technique patented by Texas A&M University colleague Robert Chapkin to examine intestinal gene expression in 22 healthy infants—12 breast-fed, 10 formula-fed. The technique involved isolating intestinal cells shed in the infants’ stools, then comparing the expression of different genes between the two groups. Mothers in the study collected fecal samples from their babies at one, two, and three months of age. Scientists then isolated genetic material from the samples. Understanding early intestinal development is important for many reasons, Donovan said. “An infant’s gut has to adapt very quickly. A new baby is coming out of a sterile environment, having received all its nutrients intravenously through the placenta. At that point, babies obviously must begin eating, either mother’s milk or formula. “They also start to become colonized with bacteria, so it’s very important that the gut learns what’s good and what’s bad. The baby’s body needs to be able to recognize a bad bacteria or a bad virus and fight it, but it also needs to recognize that even though a food protein is foreign, that protein is okay and the body doesn’t want to develop an immune response to it,” she said. If anything goes wrong at this stage, babies can develop food allergies, inflammatory bowel disease, and even asthma. “We’re very interested in frequent sampling at this early period of development,” she added. Donovan also would like to learn how bacteria in the gut differ in formula- and breast-fed babies, and this technique should make that possible. “Now we’ll be able to get a complete picture of what’s happening in an infant—from the composition of the diet to the microbes in the gut and the genes that are activated along the way.” Of potential clinical importance: The gene expressed most often in breast-fed infants is involved in the cell’s response to oxygen deprivation. Lack of oxygen is a factor in the development of necrotizing enterocolitis, a kind of gangrene of the intestine that can be fatal in premature babies and is a leading cause of disease and death in neonatal intensive care units.