New research on young twins in Malawi in sub Saharan Africa has identified a new culprit of severe acute childhood malnutrition: gut bacteria.

The latest findings, expected to be published Feb.1 in the journal Science, demonstrates how dysfunctional communities of bacteria living in the intestine work with a poor diet to trigger malnutrition.

Researchers say that the latest findings are strengthened by additional studies on mice. Researchers found that laboratory mice transplanted with the gut microbes of malnourished children experienced dramatic weight loss and altered metabolism after being fed a nutrient-poor diet.

"The gut microbes of malnourished children and malnourished mice do not appear to mature along a normal, healthy trajectory," senior author Dr. Jeffrey Gordon, director of the Center for Genome Sciences & Systems Biology, said in a statement.

Researchers found a healthy, high calorie diet only offered temporary benefits and was not enough to repair the dysfunction.

"Feeding the children and the mice a high-calorie, nutrient-rich food had a temporary, beneficial effect on their gut microbes, but not enough to repair the dysfunction," Gordon said.

"Our results suggest we need to devise new strategies to repair gut microbial communities so these children can experience healthy growth and reach their full potential," he added.

While poor diet certainly plays a critical role in childhood malnutrition, scientists have long puzzled over why only some children are affected by the condition and not others, even children in the same household and who are fed the same foods. Researchers said that this observation has led researchers to conclude that a lack of food alone cannot explain childhood malnutrition.

The recent study found that nutrient-rich therapeutic food only has a temporary effect on gut microbes. The findings show that once the therapeutic food is discontinued, the community of dysfunctional microbes in the intestine and their genes revert to an immature state in both the children and the mice.

Researchers say that the latest findings may explain why many malnourished children gain weight when they are treated with therapeutic food, but still are at high risk for stunted growth, neurological problems and even malnutrition and death after treatment is stopped.

Gordon and his team followed 317 sets of twins in Malawi for the first three years of their lives. Researchers said that during the study period, half of the twin pairs remained healthy and in the others, either one or both twins developed malnutrition.

The study focused on children who developed a form of malnutrition called kwashiorkor, an illness associated with swollen bellies, liver damage, skin ulcerations, loss of appetite and wasting.

Researchers found that malnutrition occurred just as often in fraternal twins as identical twins, which suggested that the illness is caused by another factor other than human genes.

The study also looked at the microbial genes in the gut. Gordon and his team said that these genes extract nutrients and calories from the diet, synthesize vitamins and nutrients and help shape the immune system.

Researchers tracked the gut microbes just before, during and after treatment with therapeutic food. They found that while the therapeutic food seemed to kick start the maturation of the gut microbiomes of the severely malnourished children, its benefits were only temporary. The study revealed that four weeks after the therapeutic food was discontinues, the gut microbiomes of the malnourished children either failed to progress or even regressed, while the gut bacteria of the healthy co-twins continued to mature on a normal trajectory.

Researchers conducted additional studies on mice and found that mice transplanted with malnourished children's gut microbes and that ate a poor diet experienced substantial weight loss, while those that had the healthy twin's gut microbes and ate the same nutrient-deficient diet did not.

In malnourished mice transplanted with dysfunctional gut microbes, a therapeutic diet also only produced temporary relief. Gordon and his team found that while the

microbiomes of the "malnourished" mice did mature when they were fed the therapeutic food, they tended to revert to a malnourished state when the poor diet was resumed.

Furthermore, researchers found that mice with the gut microbes transplanted from a malnourished twin also carried some species of bacteria associated with human illnesses, like inflammatory bowel disease. Researchers also found that the combination of a poor diet and dysfunctional gut bacteria altered carbohydrate and amino acid metabolism, reduced the availability of sulfur, which may contribute to weight loss, and disrupted the central metabolic pathway for extracting energy from food.

"These findings suggest that energy metabolism may be a bigger challenge for these children when they are exposed to a nutrient-deficient, low-calorie diet," Gordon said, adding that researchers plan to conduct additional studies to further their understanding of the role of the gut microbes in severe malnutrition. Researchers also hope to find ways to permanently repair the gut microbiome so sick children can overcome the long-term effects of severe malnutrition.

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