By Nicola Jones
A study transplanting gut bacteria from human twins into mice could help to explain why some malnourished children develop kwashiorkor -- a condition that triggers swelling in the belly, fatigue and vulnerability to disease. Researchers hope the work will point the way to better emergency rations for sick children.
The study, presented yesterday by Michelle Smith, a postdoc at Washington University in Saint Louis, Missouri, at the International Human Microbiome congress in Vancouver, Canada, looked at kwashiorkor in children in Malawi. The condition affects tens of thousands of children in Malawi alone and is fatal in up to 15% of cases. Although poor diet is clearly a factor, no one knows why some children are afflicted and others, living under the same conditions, are not. In tracking 317 pairs of twins in Malawi for the first three years of their lives, the group found that kwashiorkor affected both twins in a pair in only 7% of cases, and in 50% of of cases, only one of the twins.
"It's so odd, because they're living together," says Smith.
One possible explanation for why only some malnourished children fall prey to kwashiorkor is that differences in gut bacteria might affect how susceptible people are. Gut bacteria can change how people absorb iron, zinc and vitamins from their food, and have been linked to obesity (see 'Fat people harbour 'fat' microbes').
To investigate, Smith's team, working in Jeff Gordon's microbe genomics lab at Washington University, took faecal samples from some of the Malawian twins and used them to create a set of gut bacteria for mice raised in a completely clean, germ-free environment. Through this they made a near-perfect mimic of the children's gut bacteria, allowing the researchers to see how those bacteria react to changes in diet, and to do other experiments, such as faecal transplants, that would be difficult or impossible with the children themselves. "People think their faeces is just waste -- but it's really useful stuff," says Smith.
In preliminary results presented at the conference, Smith showed how mice with gut bacteria from one set of twins reacted to a series of timed diet regimes. First the mice had three weeks on a typical Malawian diet, consisting of 90% maize (corn) flour and water, and 10% vegetables; then two weeks on a diet of 'ready-to-use therapeutic food', a high-calorie peanut-butter-based food often given to malnourished children in developing countries; and finally two weeks back on the Malawian diet.
The mice with gut bacteria from the sibling with kwashiorkor were found to lose more weight on the maize-and-vegetable diet typical for Malawi, and gain more on the peanut-butter diet, than the mice with gut bacteria from the 'healthy' sibling.
Riding dietary wobbles
One possible conclusion is that the gut bacteria of the sick twin make it hard for the child to absorb the already limited nutrients and calories available in a meagre diet. The 'sick' bacteria were also much more susceptible to change -- some species flourished, while others died down, altering the overall composition of the population. The 'healthy' gut bacteria, on the other hand, were relatively stable throughout the dietary wobble.
This doesn't prove that gut bacteria composition is the key to why some children get sick and others don't. "I don't think it's not involved. But I can't say it is, yet," says Smith. James Kinross, a clinical researcher at Imperial College London, who was also at the meeting, wonders whether parasitic infections might also be a contributing cause.
But the results point the way to further studies that could help pin down the role of gut bacteria in kwashiorkor, and how they might be harnessed to help sick children. One idea is to transplant 'healthy' gut bacteria into the mice with 'sick' bacteria, and see if this makes a difference. "Their work is very important for developing countries," says Martin Blaser, a microbiologist at New York University, who was also present at Smith's talk. Their method, he adds, could be used to determine the microbiota that help people extract the maximum possible value from food.
Ultimately, Smith would like to identify a bacterium or set of bacteria that protects children from kwashiorkor, and add it to the emergency rations handed out to starving children, or give it to them beforehand. "Maybe we can do earlier interventions -- before they suffer," she says.