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Five mysteries about breast milk

This story was originally published by Knowable Magazine.

A mother’s milk, rich in an exquisitely tailored mix of fats,
proteins, vitamins and minerals, provides all the nutrition a
helpless infant requires — and more. Breast milk is thought to
protect against disease, set up a healthy digestive system and
even influence a child’s
. And yet we know a lot less about this important
substance than we could, says lactation researcher Katie Hinde of
Arizona State University.

In a 2016 talk, Hinde noted that more studies are done on coffee,
wine or tomatoes
than on human breast milk. (The scholarly
database Web of Science identified about 1,200 scientific articles
published in 2017 for the search term “breast milk,” compared with
almost 3,500 for “tomatoes.”) “Breast milk,” Hinde says, “has not
been a research priority.”

But the research is picking up. Here are five mysteries about
breast milk that scientists are working to understand.

Nursing sick babies

It’s well-established that human milk (as well as the fluid
known as colostrum that mothers produce the first days after birth)
carries protective factors such as antibodies to help a baby stave
off infections. But research suggests that immune components in
milk might ramp up when babies need them most. A 2013 study found
that when mothers and babies both had
, levels of white blood cells in milk jumped by a factor
of 64. But even when just the babies were sick, levels of white
blood cells still increased 13 times. “That’s quite a big
increase,” says the study’s lead author, Foteini Kakulas (formerly
Hassiotou), a cell biologist and lactation researcher at the
University of Western Australia.

Research suggests that immune
components in milk might ramp up when babies need them most.

A second study found that lactoferrin — an immune molecule that
performs a variety of protective functions, such as puncturing the
walls of harmful bacteria — was elevated in the weeks before and after
an infant was sick
. Once again, mothers did not report being
sick, though the authors write that there was “almost certainly”
underreporting of illness from moms.

How might this work? The most likely explanation is that infant
saliva traveling back through the mother’s breast ducts carries a status report on the
baby’s health
, says Kakulas. “When baby saliva is transferred
back into the breast … it’s very logical that the pathogen that is
driving the sickness would be transferred too.”

Front- and side-view cutaways of a human breast. A third figure shows a group of alveoli connected to milk ducts.

These 19th century illustrations hint at the internal workings
of the breasts. Milk is made and stored in the alveoli, depicted as
clumps of white spheres. Branching milk ducts carry milk from the
alveoli to the nipple. Lymphatic vessels (on the left, in Figure 1)
also lace through the breast tissue, carrying fluids and


Sleep signals in milk

As new parents know well, babies don’t come with built-in sleep
schedules. Could breast milk help to set them? Both the sleep
hormone, melatonin, and its precursor, tryptophan, are present in
human breast milk and both seem to fluctuate on a cycle that might
help babies sleep or wake. A 2016 study found that melatonin levels
were, on average, nearly five times higher in breast milk
produced at night than during the day

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Another report, in 2017, found that levels of the hormones
cortisone and cortisol were higher in
morning breast milk
than in milk produced in the afternoon,
evening and night. Both cortisone and cortisol are involved in the
body’s stress response, and cortisol serves to kick-start our
physiology when it’s time to wake.

But it still isn’t clear whether these signals actually allow a
mother’s daily rhythm to shape her baby’s sleep-wake cycle, says
Hinde. Also unclear is what a lack of these chemicals might mean
for formula-fed babies, or what may happen to sleep patterns if
babies drink milk pumped at another time of day. “We know that
babies have the receptors for these hormones in their bodies, that
the hormones coming from the mother are binding to receptors in the
baby,” she says. “But what does it mean if they aren’t getting that
signal? We don’t know.”

Eating for the gut microbiome

Breast milk isn’t food just for babies — it’s food for trillions
of microbes that set up camp in their digestive systems, a
community dubbed
the human gut microbiome
. Recent research suggests that
breast milk may have evolved to
promote the growth of microbes that help keep babies

Breast milk isn’t food just for
babies — it’s food for trillions of microbes that set up camp in
their digestive systems

“The third-largest constituent in breast milk is not there to
feed the babies — it’s there to feed the microbes,” says
microbiologist David Mills of the University of California, Davis.
He’s referring to human milk oligosaccharides, complex chains of
sugars found in breast milk. (Mills has established a probiotic
company based on his research.) These complex sugars bolster the kinds of intestinal
that can digest the compounds into short-chain fatty
acids — ones that babies need to thrive.

It’s not yet clear what defines a healthy infant gut microbiome,
or how that system changes as babies develop. And scientists
disagree on how the microbiome is set up to begin with: Are key
microbes delivered to the newborn’s uncolonized gut via breast
milk, or do they come in from other sources such as amniotic fluid
or the mother’s skin?

Variations in milk

All breast milk is not created equal: It can vary in levels of
proteins, fats, sugars, hormones and other components. But breast
milk doesn’t just differ from mother to mother. It can also differ
when the same mother nurses different babies, and across the span
of an infant’s development.

It also may shift depending on a baby’s sex. Working with rhesus
monkeys, Hinde found that that mothers make more milk for female offspring, but milk
richer in fat for male offspring
. She saw similar sex differences when she
pored over the lactation records of more than a million cows.

If these kinds of differences translate to human milk,
understanding them could help optimize formula or donor milk for
babies who don’t have access to their own mother’s milk, Hinde
says. But scientists have only begun to characterize this variation
and the factors that drive it.

A dash of stem cells

In 2007, scientists discovered an unexpected ingredient in human
breast milk: stem cells. These cells retain flexibility that most
adult cells have lost and can form a broad variety of tissues. In a
2014 study, scientists tracked individual stem cells from the
mammaries of nursing mice. They found that the cells crossed the
pups’ stomach walls into circulation and lodged themselves into
developing tissues throughout their bodies. When the baby mice grew
up, the mothers’ cells were still
and had turned into mature tissues alongside the babies’
own cells.

Organoids in a dish

Stem cells extracted from breast milk take on their own life in
the laboratory, forming organ-like blobs reminiscent of the
breast’s milk-producing alveoli. Like alveoli, these lab-grown
organoids can make milk. 


In a lab dish, scientists have grown stem cells extracted from
human breast milk and coaxed them to form organ-like blobs that
have spherical endings reminiscent of the alveoli that make up the
mammary glands. These organoids could even produce milk.

No one yet knows how these cells affect infant development or
what happens to babies who don’t get them — another mystery to add
to the things-we’d-like-to-know list.

This story was originally published by Knowable Magazine. Knowable Magazine is an independent journalistic endeavor from Annual Reviews.

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