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Wed January 30, 2013

Gut Microbes May Play Deadly Role In Malnutrition

Originally published on Mon September 9, 2013 8:44 am

There's a part of our body that's only now getting mapped: the trillions of microbes, mostly bacteria, that live in our guts.

Some scientists describe this community as a previously unnoticed vital organ. It appears to play a role in how quickly we gain weight and how well we fight off disease.

A study published in the journal Science suggests that changes in this community of microbes also may cause kwashiorkor, a kind of deadly malnutrition.

If you've seen the horrifying pictures of famine — listless children with swollen bellies — you've seen the face of kwashiorkor. It's not the most common form of malnutrition, but it is the most deadly. It can hit a child quickly.

Nutritionist Rebecca Stoltzfus, who directs the international nutrition program at Cornell University, says there's something baffling about this disease. Some children get it, while others, who seem to be eating the same diet, do not.

"What causes some malnourished children to transition into kwashiorkor, remarkably, remains a mystery after all these years," she says.

Many scientists, she says, suspect that there's something going on inside the gut. But what?

Enter Jeffrey Gordon, from the med school at Washington University in St. Louis. Gordon has pioneered studies of such microbial communities — what scientists now call the microbiome — and how this microbial community affects conditions such as obesity.

Gordon decided to take on kwashiorkor. He joined forces with other scientists who were already working in Malawi, a country in southern Africa where malnutrition is common.

They decided to study twins, so that they could compare children who were genetically similar, and living in similar environments.

"We recruited a group of 300 twin pairs, identical and fraternal, and followed them through their first three years of life," he explains.

None of these twins, at the beginning, were malnourished. But when they came back for checkups, a pattern emerged in almost half of the pairs of twins: "One twin, in the pair, remained healthy, and the other twin developed either moderate or severe malnutrition."

These children immediately were treated with therapeutic food. But before they were treated, and again afterwards, for several weeks, the scientists took samples of their feces, to study the bacteria that lived in the gut.

Gordon says, the children with kwashiorkor had a different population of microbes than their healthy twins. During treatment, a healthy community of microbes started to emerge, but the improvement didn't last.

It was clear evidence that this abnormal community of microbes was associated with malnutrition. But could it actually be the cause of their disease?

Gordon wanted to see if these microbes caused similar symptoms in laboratory mice. So he transplanted samples of the microbial communities from just three pairs of twins into special strains of mice that were raised in completely sterile conditions. Their bodies contained no other microbes.

The mice got food similar to what children eat in Malawi. And in two out of three cases, the mice that got microbes from the sick children started to lose weight.

Gordon says, it suggests that down the road, we might be able to treat severe malnutrition with better food and also new intestinal microbes. "Next-generation probiotics!" he says.

Other scientists aren't ready to go that far.

First of all, it's impossible to draw many firm conclusions from observations of just two or three pairs of mice. Even though the mice lost weight, you can't say they had kwashiorkor. And finally, we're a long, long way from a probiotic treatment.

But they agreed that this hint of a link between microbes and severe malnutrition is intriguing and worth pursuing further.

Stoltzfus, meanwhile, was struck by something else in Gordon's study. "The twin study makes it all the more perplexing: How did these babies get so different?" she asks.

They were genetically the same, growing up in the same home. Yet it was generally just one child in a pair of twins who had kwashiorkor — rarely both twins together.

"How are these babies being cared for? What's going on between these twins? How are they having such different life experiences," Stoltzfus asks. Answering such questions, she says, means getting into homes and understanding how families work.

It's something we can do right away, she says. And it might prevent kwashiorkor from developing in the first place.

Copyright 2014 NPR. To see more, visit http://www.npr.org/.

Transcript

AUDIE CORNISH, HOST:

There's a part of our biology that's only now being explored. It is the trillions of microbes, mostly bacteria, that live in our guts. Some scientists say, taken together, these microbes are like a vital organ. They play a role in how quickly we gain weight and how often we get sick. A new study released today by the journal Science suggests they may also cause a kind of deadly malnutrition. Here's NPR's Dan Charles to tell us about it.

DAN CHARLES, BYLINE: If you've seen the horrifying pictures of famine - listless children with swollen bellies - that's the face of a disease called kwashiorkor. It's not the most prevalent kind of malnutrition, but it's the most deadly. It can hit a child quickly.

And Rebecca Stoltzfus, a specialist in nutrition at Cornell University in New York, says there's something baffling about this disease. Some children get it while others, who seem to be eating the same diet, do not.

REBECCA STOLTZFUS: What causes some malnourished children to transition into kwashiorkor remarkably remains a mystery after all these years.

CHARLES: There are suspicions, she says. A lot of people think there's something going on in the gut. There are now new tools for studying that. And Jeffrey Gordon, from the school of medicine at Washington University in St. Louis, invented a lot of those tools. So Gordon decided to investigate kwashiokor.

JEFFREY GORDON: We turned to a country where malnutrition, tragically, is all too common a problem.

CHARLES: The country of Malawi in southern Africa. He and his collaborators decided to study twins so they could compare children who were genetically similar and living in similar environments.

GORDON: We recruited a group of over 300 twin pairs, identical and fraternal, and followed them in their first three years of life.

CHARLES: None of these twins at the beginning were malnourished. But when they came back for checkups, a pattern emerged in almost half of the pairs of twins.

GORDON: One twin remained healthy in the pair and one twin developed either moderate or severe acute malnutrition.

CHARLES: These children immediately got concentrated therapeutic food. But before they were treated, and then for several weeks afterward, the scientists took samples of their feces to study the makeup of the bacteria that lived in the gut. Gordon says the children with kwashiorkor had a different population of microbes than their healthy twins. Treatment with better food did start to create a healthier community of microbes, but the improvement didn't last. And Gordon wondered, could this abnormal community of microbes actually be causing kwashiorkor in these children? How could he test that?

GORDON: Could we transmit some features of their disease via their microbial community to mice that had been raised under entirely sterile conditions?

CHARLES: He transplanted samples of the microbes from just three pairs of twins into mice. The mice got food similar to what children in Malawi eat. And in two out of the three cases, mice that got microbes from the sick children started to lose weight. It makes Gordon think that maybe down the road we might be able to treat severe malnutrition with better food and also new intestinal microbes.

GORDON: Next-generation probiotics.

CHARLES: Now, other scientists aren't ready to go that far. A couple of mice losing weight is not very strong evidence, they say. But they agree this hint of a link between microbes and malnutrition is certainly worth pursuing. Cornell University's Rebecca Stoltzfus, meanwhile, was struck by something else in Gordon's study.

STOLTZFUS: The twin study makes it all the more perplexing. Well, then how did these babies get so different?

CHARLES: They're genetically the same, growing up in the same home, yet it was generally just one child who had kwashiorkor, rarely both twins together.

STOLTZFUS: How are these babies being cared for? What's going on between these two twins? How are they having such different life experiences?

CHARLES: Stoltzfus says figuring this out means getting into homes and understanding how families work. This is something we can do right away, she says, and it might prevent kwashiorkor in the first place. Dan Charles, NPR News.

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