8/13/2018 BBC - Future - How bacteria can save children’s lives

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How bacteria can save children’s lives

A ground-breaking new project in Bangladesh could help reduce the life-long

health problems that come from childhood malnourishment – by focusing on the
gut.

By David Robson
9 August 2018

For decades, undernourished infants across the world have been treated with a course of high-calorie,
high-protein rich foods. The foods may come in various forms – from peanut-rich pastes to fatty
milkshakes – but the common-sense philosophy is always the same: restore the most basic nutrients
to the growing body as quickly as possible.

These “ready-to-use therapeutic foods” help to remove the immediate danger to the child’s life.
But the battle is only half-won.

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The period of undernourishment may be for just a few months, but consequences can last a lifetime.
Throughout childhood and adolescence, the child will remain physically stunted and more
vulnerable to infection. He or she also may show cognitive deficits, resulting in lower IQs, and
reduced impulse control – which can mean falling behind at school and struggling to find
employment as an adult.

We may be overlooking a key potential

solution: friendly bacteria

But ground-breaking new research suggests that we may be overlooking a key potential solution: the
tens of trillions of friendly bacteria living in our digestive tract, together known as the gut microbiota.
“We are a sublime mixture of human and microbial parts,” says Jeffrey Gordon, the director of the
Center for Genome Science and Systems Biology at Washington University in St Louis – and these
teeming communities of invisible allies are now thought to be essential for our health and well-being.
The gut microbiota is so important, in fact, that scientists such as Gordon often refer to it as a separate
‘organ’.

According to Gordon’s theory, many of the long-term consequences of malnutrition can be directly
linked to a disruption of the gut microbiota. And by correcting that imbalance, you may be able to
nudge a child’s growth back on the right path.

Funded by the Bill and Melinda Gates Foundation, Gordon has been leading pioneering studies in
Malawi and Bangladesh to test the truth of this idea. And the early results look promising.

A better approach cannot come soon enough. More than 200 million children under five currently
suffer from undernourishment.

The seeds of this new understanding can be found in a study by the South African doctor PM
Smythe, first published in The Lancet in 1958. The exact role of our gut microbes in our health was
still largely unknown at this time, but there was an emerging realisation that the mix was important –
with some species helping to synthesise important nutrients and others consuming valuable resources
before the host could absorb them.

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With this in mind, Smythe decided to examine children with kwashiorkor – a form of undernourishment
that typically arises from a lack of protein, leading to fluid retention around the abdomen and a
noticeably distended belly. Sure enough, he found that the pattern of species throughout the intestine
was different for the children with kwashiorkor. In the stomach, for instance, he found several species
of bacteria that normally inhabited the large intestine. This suggested that an imbalance in their gut
microbiota might be linked to their weight loss. “The observation supported Smythe’s hypothesis that
altered gut microbial communities might potentially contribute to the clinical picture of severe
undernutrition,” explains Geoffrey Preidis at the paediatrics department of Baylor College of Medicine
in Texas.

Crucially, Smythe also trialled treatments to restore the correct balance, giving the children antibiotics
to reduce the colonisation of harmful bacteria and probiotic yogurts that aimed to seed the gut with the
helpful species. The result, he reported, was a more rapid recovery.

It was only a small trial, however. A later attempt to replicate his particular treatment failed to show
similar benefits. Scientists like Smythe also were limited by the technology of the day. They could
only identify the relevant species of microbe by taking biological samples and then cultivating the
bacteria in vitro – a laborious process.

Advances in genetic screening have now made this process a lot easier. “Today, we don’t have to
grow bacteria to study them – we can determine which microbes are present in a sample just by
sequencing their DNA,” says Preidis. “This is important because the vast majority of gut microbes are
difficult to grow in the laboratory.” The availability of easy study methods has led, in turn, to a
blossoming of new research on the many ways our gut microbiota can influence our health.

Species of ‘good’ bacteria such as Lactobacillus and Bifidobacterium can reduce inflammation and
strengthen the gut barrier, for instance. They can also help to break down complex carbohydrates
and proteins. Crucially, these good bacteria also aid the production and absorption of amino acids that
are essential for growth. Given that the growing brain is one of the body’s hungriest organs, these
benefits could be essential for healthy neural development.

A diverse gut microbiota can strengthen you

against infections

Even more importantly, a diverse gut microbiota can strengthen you against infections such as
shigella, listeria or salmonella. This is partly due to competition: the established bacteria make it

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harder for the pathogens to find a niche and thrive. A larger number of helpful – or at least, harmless –
bacteria could also stimulate the immune system, which should also help us fight off infection from
more damaging species.

If a poor diet reduces these natural defences, then undernourished children could quickly enter a
vicious cycle, explains Jonathan Swann, an associate professor in microbiomics at Imperial College
London. “Children who are undernourished often live in environments where they are exposed to a
large amount of pathogens,” he says. “And this additive effect of greater pathogen exposure and
reduced ability to clear them leads to more persistent infections, which can drive prolonged
diarrhoea and leads to chronic inflammation of the gut. This, in turn, damages the gut structure and
impairs its function.” The result would be further undernourishment, leading to stunting and cognitive
deficits.

Worse still, they are also missing the microbes necessary to break down any food they do receive.
“The microbiota is not able to finish the digestion – so first, they don’t have enough food, and then,
they can’t digest the food you do give to them,” says Didier Raoult at the Aix-Marseille Universite, who
studies kwashiorkor.

It’s clear that many plausible mechanisms exist through which an impoverished gut microbiota could
contribute to the lingering long-term effects of malnutrition. The real challenge for Gordon has been to
establish more direct evidence that the one causes the other.

Much of this research has taken place in Dhaka, Bangladesh and Malawi. Gordon is still moved by the
close cooperation of the local doctors and nurses and by the families of the affected children who,
despite their hardships, must take regular trips to the hospital to contribute to the project.

“The trust and the devotion of the mothers for their children are enormous at these sites,” he says.
“And the trust they have in the healthcare providers is extraordinary and truly inspiring.”

One such study involved taking monthly faecal samples of children who had suffered periods of acute
undernourishment. Using an advanced algorithm to sequence genetic material within the sample, the
team identified 24 key species that appeared to be associated with healthy growth and compared their
abundance in the two groups. Sure enough, they found the microbiota of healthy children evolved over
time, while the microbiota of the undernourished children seemed to stay in an “immature” state,
with less overall diversity and less ability to produce and absorb the nutrients they needed at each
stage of their growth.

Crucially, the standard therapeutic foods failed to repair the balance in the long term. “So the children
were walking around with a persistent developmental problem affecting their ‘microbial organ’,” says

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Gordon.

To prove the long-term consequences of this, Gordon next created a group of “gnotobiotic” mice,
raised in extremely sterile conditions so that their bodies lack their own microbiota. He implanted these
“empty vessels” with the gut microbiota of children who had and hadn’t developed the symptoms of
undernourishment, such as stunting. This allowed the researchers to isolate the effects of the microbial
diversity on the mice’s long-term growth and development while controlling all other factors.

In one of the first papers to use this technique, Gordon’s post-doctoral student Laura Blanton showed
that the mice receiving the samples from the undernourished children experienced stunted
growth compared with those receiving the samples from the healthier children. This confirmed the idea
that the imbalanced microbiota can be a cause of the long-term developmental problems.

Gordon’s team have recently found similar results using gnotobiotic piglets, the biology of which is
even closer to the human body. Once again, the state of their gut microbes predicted the piglets’ long-
term prospects.

These findings have already won widespread acclaim, helping Gordon to earn the Royal Society’s
prestigious Copley Medal earlier this year – a prize previously bestowed on the likes of Dorothy
Hodgkin, who deciphered the structure of the hormone insulin, and Albert Einstein.

There is still much more work to be done. Preidis, for instance, points out that we still need to
understand the exact chain of events that leads a child’s body into the vicious cycle of
undernourishment and infection.

But given these strong associations, Gordon’s team is already looking for potential treatments
designed to correct the imbalances in the child’s microbiota and restore healthy growth before it is too
late. Taking place in Dhaka, the project is again a close collaboration with the local community to
identify a therapeutic food that would be suitably adapted to the child and mother’s tastes, culturally
acceptable, and potentially beneficial to the local economy.

They started by examining the foods given to the child during the weaning period, in case these might
offer any hints about components that may be more or less beneficial. “We hypothesised that over the
generations, mothers have made insightful observations linking certain foods to healthy growth,” he
says. “We wanted to mine this inventory of affordable and available complementary foods, much like
you would search a library, to identify ingredient combinations that could repair defective microbial
community development in malnourished children.” The team then whittled down that list to develop
new therapeutic foods and conducted short-term studies to test their effectiveness in restoring the
development of the microbiota.

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Gordon discussed some of his early results at the Society for Neuroscience meeting in Washington,
DC in November 2017, and the team has recently submitted a paper to a journal. He is wary of
disclosing too many of the details until they have passed through the rigours of peer-review – a
standard process in which a new finding is subject to the scrutiny of other scientists. But he confirms
that they look “promising.”

Gordon’s caution is understandable. Humans have spent millennia getting to grips with the human
body, while the study of our invisible “microbial organ” still has a long way to catch up. We are only just
beginning to understand the importance of that organ and the ways to encourage its long-term health.
But if the treatments currently being tested do work, they could be a vital first step toward relieving
millions of people’s suffering. As Gordon puts it: “this is just the beginning of the journey.”

--

David Robson is a science writer based in the UK. He is @d_a_robson on Twitter.

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