In a study published February 18 in Cell, a team led
by Jeffrey Gordon at the Washington University
School of Medicine in St. Louis now finds key
components in breast milk that promote healthy
infant growth and how interactions with the gut
bacteria drive this process.
Di
Anton Nossik - TheKid, CC BY 3.0,
Partnering with colleagues in Malawi, Africa, where
almost half of all children under five show stunted
growth, the study's researchers obtained small
samples of human breast milk from the mothers of
healthy or stunted babies. They found that sugars
containing sialic acid, which has been implicated in
brain development, were far more abundant in the
breast milk of mothers with healthy compared with
stunted babies.
This
suggested that these breast milk sugars might
promote healthy infant growth. To determine if this
was the case, the researchers established animal
models that allowed both diet and the gut microbiome
to be manipulated, since they found in a related
study published concurrently in Science that gut
microbes are important mediators of normal growth.
Gordon and his team introduced a collection of
bacterial strains isolated from the fecal sample of
an undernourished infant into mice or piglets. The
researchers then fed the animals a prototypical
Malawian diet consisting of corn, legumes,
vegetables, and fruit, which on its own is
insufficient for healthy growth.
With
both the diet and microbiome mimicking those of
undernourished Malawian infants transitioning to
solid foods, the researchers then tested the effects
of sialylated sugars. Given the difficulty of
purifying large quantities of compounds from human
breast milk, they turned instead to cow's milk,
which contains sialylated sugars, but at 20-fold
lower concentration than in breast milk. Through a
complex series of steps, they isolated sialylated
sugars from whey, a byproduct of cheesemaking, and
fed it to the animals. Remarkably, the animals
showed substantial improvements in growth, with
increases in lean body mass and bone volume as well
as metabolic changes in the liver, muscle, and brain
suggesting improved ability to mobilize nutrients
under diverse conditions. Crucially, these effects
depended on the presence of the gut microbiota.
Since
the assortment of gut bacteria that were isolated in
this study were defined and could be grown in a
dish, the authors were then able to tease out which
bacteria were affected by sialylated sugars and how
the different strains interacted with one another.
They found that one species of bacteria fed on
sialylated sugars, while another in turn fed on the
digested products of those sugars, pointing to a
food web among the bacterial community living in the
gut. However, these two bacterial strains alone were
not able to support healthy growth in mice; instead,
more complex interactions between different types of
gut bacteria were needed to promote growth.
This
study lays the groundwork for identifying the
components of breast milk that are needed for infant
health and how they interact with the gut microbiome
and other dietary components. The authors are
excited to extend the approach to look at other
mothers and babies to see how general their
observations are. "This capacity to look in a very
controlled way at how food is partitioned among
members of a microbial community and how the
metabolic output of that community can affect human
biology is part of our ongoing agenda," Gordon says.
One
possible application that may stem out of this work
is improving infant formulas as well as therapeutic
foods used to treat undernutrition, both of which
are currently based on cow's milk and are therefore
deficient in sialylated sugars. The researchers are
hopeful, but careful to point out that more needs to
be learned about how different types of bacteria
interact with components of breast milk and
complementary foods, and to ensure that harmful gut
bacteria would not thrive on those components and
thereby gain an advantage over beneficial microbes.
"Even
though our intentions are good, we want to make sure
we do no harm," Gordon says. "This is just the
beginning of a long journey, an effort to understand
how healthy growth is related to normal development
of the gut microbiota, and how we can establish
whether durable repair of microbiota immaturity may
provide better clinical outcomes."
For
more information
Cell, Charbonneau et al.
Sialylated Milk Oligosaccharides Promote
Microbiota-Dependent Growth in Models of Infant
Undernutrition
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