Breast milk science

Breast milk science: unravelling the complexity

“Breast is best”, so the mantra on infant feeding goes. The evolutionary case for that logic is easy — human milk is designed to feed human infants. But unravelling the chemistry that underpins the benefits of breast feeding versus using infant formula is still an adventure in complexity.

As researchers tease apart the roles of sugar, protein, and fat in milk, as well as the roles of beneficial gut microbes that help process the milk in babies’ tummies, they are finding many interrelated ways in which milk nourishes infants and protects their health.

One example is sugars. The most abundant sugar in human milk is the disaccharide lactose, from which babies derive energy. But breast milk also contains complex polymeric sugars called oligosaccharides that babies can’t break down. Oligosaccharides are metabolically costly to produce, and it makes no sense for mothers to make them if they don’t play an important role in infant survival, says David A. Mills, a food science professor at the University of California, Davis.

Mills and his UC Davis colleagues have spent a decade developing a program to better understand breast milk, which has expanded from studying sugars to running clinical trials on infants and developing nutritional supplements.

The oligosaccharides are difficult to analyze, requiring new analytical methods using state-of-the-art lab instrumentation. UC Davis chemistry professor Carlito B Lebrilla, for example, has developed a high-throughput liquid chromatography/mass spectrometry approach to separate, identify, and quantify about 200 oligosaccharides in milk.

In collaboration with Mark A Underwood, a professor of pediatric neonatology at UC Davis Children’s Hospital, Lebrilla and colleagues use feeding tubes that allow them to sample stomach contents to track which oligosaccharides get digested quickly in babies. They can also do what UC Davis food science professor J. Bruce German calls “diaper diagnostics,” taking a look at pee and poop to compare what goes into a baby with what comes out (Anal. Bioanal. Chem. 2013, DOI: 10.1007/s00216-013-6817-1).

In the long term, this combination of approaches could provide ways to diagnose digestive problems in babies, Lebrilla says.

It turns out that the major role of oligosaccharides in human milk is to serve as food for beneficial gut microbes. In particular, Bifidobacterium longum subsp. infantis appears to have coevolved with humans specifically to feed on the oligosaccharides. Genomic and biochemical studies in Mills’s lab have pinpointed the various genes and proteins that enable B infantis to consume milk oligosaccharides (Microbiology 2013, DOI:10.1099/mic.0.064113-0).

Additionally, some of the cell wall proteins produced by B infantis appear to have dual roles: They enable the bacteria to capture milk oligosaccharides for food and latch onto sugars residing on the cell walls of an infant’s intestines. Those capabilities enable B infantis to outcompete and prevent colonisation by other microbes, such as harmful Escherichia coli strains.

Capitalising on what they’ve learned so far, the UC Davis breast milk researchers are developing B infantis probiotics that could be used as nutritional supplements. And they are conducting clinical trials to see if the probiotics can improve the health of premature babies in neonatal intensive care units.

Studies elsewhere have already demonstrated that some probiotics support infant health. But those products have been prepared from bacterial strains that are easy to grow and generally thought to be health-promoting for adults, Underwood says. Instead, he and his colleagues are focusing on B infantis, which is difficult to grow in a petri dish but clearly plays an important role in the intestines of healthy newborns.

For premature babies in particular, Underwood hopes the probiotics will help prevent necrotising enterocolitis, a destructive intestinal disease that affects roughly 10% of premature babies. About 25% of the babies who contract the severe form of the disease die.

Doctors believe the disease is caused by pathogenic bacteria getting into the lining of the intestines. “When we compare the fecal composition of bacteria in a premature infant with a full-term infant, they are very different,” Underwood says. “The idea behind the probiotic is to try to give preemies more of the bacteria that we find in healthy term babies.”

To give B infantis the best chance to thrive and keep pathogenic microbes at bay, the beneficial microbes must have the necessary oligosaccharides for food. For infants unable to get breast milk, the oligosaccharides have to come in the form of a prebiotic — a dose of oligosaccharides that could be added to formula…..

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