Miracle food: Unraveling the mysteries of mother's milk
"Premature babies who receive human milk have about one-half the rate of necrotizing enterocolitis, one of the most dangerous complications that we commonly see in the NICU."
It’s the perfect food. Backed by millions of years of evolution, it’s a complex blend of fat, protein, sugars, minerals and antibodies. Doctors recommend that we live on it and nothing else for at least six months of our lives. The miracle food? Human breast milk, of course.
Neonatologist Mark Underwood cares for premature newborns in the Neonatal Intensive Care Unit (NICU) at UC Davis Children’s Hospital and is a strong advocate of mother’s milk to feed this most vulnerable population.
"Breastfed infants have a lower risk of developing a whole host of infections, from colds to ear infections to pneumonia," says Underwood, who conducts clinical trials aimed at determining the best food for premature infants. "And premature babies who receive human milk have about one-half the rate of necrotizing enterocolitis, one of the most dangerous complications that we commonly see in the NICU."
Necrotizing enterocolitis, called "NEC" for short, spreads and inflames the intestinal tract, sometimes destroying tissue as it goes. Many infants can be treated with antibiotics in the hospital, but some require surgery to remove part of the bowel. About a quarter of infants who develop it die from the disease, and others may be left with lifelong difficulties – from poor growth due to malabsorption to motor and intellectual problems.
NEC typically develops within the first few weeks of life when a premature infant starts eating and the gastrointestinal tract rapidly becomes populated by a large quantity and variety of bacteria. How breast milk protects babies from developing NEC is a question that fascinates Underwood along with multiple collaborators from diverse departments across the UC Davis campus. They are analyzing breast milk in exciting new ways and coming up with some remarkable discoveries.
A formula like no other
Breast milk contains about 70 g/L of lactose, 40 g/L of fat and 8 g/L of protein, a recipe that provides essential nutrition to a growing infant and can easily be replicated in infant formulas. But a significant component (up to 15 g/L) is oligosaccharides – chains of from three to 15 simple sugars. Despite their substantial presence, human milk oligosaccharides (HMOs) are actually indigestible and have no nutritive value to the baby. Why are they there?
Researcher Carlito Lebrilla, distinguished professor of biochemistry and molecular medicine, has paved the way to figure this out by developing sophisticated high-throughput mass spectrometry techniques to identify the structures of HMOs in breast milk, as well as in an infant’s blood, urine and feces. He has characterized more than 200 different HMO structures in breast milk, with each mother producing about 150 varieties.
To try to determine the function of HMOs in an infant’s intestine, Lebrilla’s team, collaborating with UC Davis colleagues David Mills and Bruce German, provided HMOs as the sole source of nutrition in a growth medium to a host of disease-causing bacteria, including Escherichia coli (E.coli) and Staphylococcus aureus, as well as Clostridium, lactobacillus, streptococcus and enterococcus species. Nothing survived. Instead, what thrived in the HMO soup was Bifidobacterium infantis, a bacterium dominant in the gastrointestinal tract of many healthy breastfed babies, and which formula-fed babies have at lower levels.
"HMOs in breast milk appear to provide an environment that allows Bifido to populate the infant’s gut and outcompete the bad guys," says Lebrilla. "Although HMOs provide no direct nutrition to the baby, they play an extremely important role in shaping the intestinal microflora to protect against infectious diseases."
Lebrilla’s group also is unraveling the reasons for the diversity of HMOs produced by different mothers as well as by individuals over a span of time.
"HMOs in breast milk appear to provide an environment that allows Bifido to populate the infant’s gut and outcompete the bad guys. Although HMOs provide no direct nutrition to the baby, they play an extremely important role in shaping the intestinal microflora to protect against infectious diseases."
They and their collaborators have found that the patterns of HMO structures depend both upon maternal genetics and diet, and furthermore, that different strains of Bifidobacteria have definite preferences for which HMOs they eat.
"Mothers appear to be selecting specific groups of bacteria, and the makeup of this group varies as the infant develops," Lebrilla adds. "We also have evidence that certain HMOs directly block the binding of pathogens to the intestinal mucosa, thereby serving as a rudimentary immune system."
The UC Davis group that is focused on breast milk has obtained more than $20 million in funding during the past 10 years and has generated more than 200 publications. Their findings, due in large part to Lebrilla’s development of techniques to analyze HMOs, have spurred new research interest in breast milk nationwide with offshoots into areas exploring the use of analogs of breast milk components for nutritional supplements for infants as well as for adults with gastrointestinal problems.
Lebrilla credits the wide and deep expertise and collaborative atmosphere at UC Davis for its emergence as the world leader in breast milk research.
"We are delighted that the UC Davis group is exploring HMOs in human milk and generating excitement about its antimicrobial properties," says Gilman Grave, chief of the Pediatric Growth and Nutrition Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
"Their work has many ramifications, not only to basic science but to applied medicine and to the development of pharmaceuticals."
Translational applications are already in the works. Several members of the UC Davis group have helped launch a company aimed at delivering the probiotics to at-risk infants.
Another project that the group is working on is establishing a breast milk bank at UC Davis. The number of milk banks in North America is very low compared to South America and Europe. The Human Milk Banking Association of North America has only one site in California. Under strict regulation, donor breast milk from banks is safe and healthier for premature babies than formula. For these vulnerable infants, it can be life-saving, but adequate availability is a constant problem.
Underwood envisions tremendous advantages to the babies in the NICU and to the local community of having a steadier supply of human milk for babies whose mothers cannot provide their own milk.
But the advantages would stretch far beyond the Sacramento area.
Underwood is confident that his colleagues on campus could develop a better milk pasteurization method that could be adopted by milk banks worldwide. Current techniques, while critical for killing dangerous bacteria, also destroy protective biological molecules.
A milk bank on campus would also greatly expand opportunities for research. With permission from donors, Lebrilla anticipates having ready access to a much larger number and variety of milk samples for analytical testing.
In the meantime, Underwood, Lebrilla and other researchers at UC Davis focused on breast milk are leading the search to unlock the mysteries of nature’s most important food.
"Milk used to be the Rodney Dangerfield of body fluids," laughs Lebrilla, referring to the comedian famous for his catchphrase, ‘I don’t get no respect.’ "Today the situation is quite different."