A new approach targeting childhood malnutrition has had promising results in a clinical trial of malnourished children in Bangladesh. The global team of researchers from the Washington University School of Medicine in St. Louis and the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh have identified microbiota-directed complementary foods (MDCFs) to treat children with acute malnutrition. The food was designed to develop a mature gut microbial community, necessary for proper growth and functioning, in the digestive tracts damaged by acute childhood malnutrition.
The work is published in two back-to-back papers today in Science. They are the “Effects of microbiota-directed foods in gnotobiotic animals and undernourished children” and “A sparse covarying unit that describes healthy and impaired human gut microbiota development“, both of which are led by Jeffrey Gordon, MD, the Robert J. Glaser distinguished university professor in the department of pathology and immunology at the Washington University School of Medicine in St. Louis (WUSTL) and a pioneer in the microbiome field.
“We found that children who are malnourished have incompletely formed gut microbial communities compared with their healthy counterparts,” said Gordon. “Therefore, we set about to design therapeutic foods to repair this immaturity and to determine whether such repair would restore healthy growth.”
Using a “statistical approach initially applied to financial markets”, the researchers determined the main types of bacteria (named an “ecogroup”) present in the healthy gut of Bangladeshi children ages one to 60 months. In a series of experiments in mice and pigs with bacteria-free digestive tracts, they identified which sets of foods were associated with certain bacterial communities, and which could move an immature gut microbiota toward a mature configuration that could support a child’s growth after severe malnutrition. Their findings suggest that protein-rich plant foods such as chickpeas, bananas, and peanut flours support this microbial transition.
The clinical trial, led by Tahmeed Ahmed, PhD, the International Centre for Diarrhoeal Disease Research’s director of nutrition and clinical services, included 63 Bangladeshi children, 12–18 months of age, diagnosed with moderate acute malnutrition (MAM), meaning the children were ill but not close to death. The children were randomly assigned to one of four treatment groups. Children in three of the groups each received one of the three newly designed therapeutic foods, while those in the fourth group received a standard therapeutic food.
One of the therapeutic foods stood out from the rest, even in this relatively short one-month trial. Measuring 1,300 blood proteins, including those intimately involved in directing bone growth, development of the brain, immune function, and metabolism in various tissues, revealed that this food prototype had produced a pronounced shift toward a healthy state compared with what was observed in the other three groups of children.
At the end of the study, the researchers found that, unlike in the three other treatment groups, the gut microbial communities residing in the intestines of children receiving this lead therapeutic food had undergone a reconfiguration and more closely resembled microbial communities found in age-matched healthy children living in the same locale. This formulation contained, among other components, a mixture of nutrients from chickpea, soy, bananas, and peanuts.
Childhood malnutrition is a massive global health problem, affecting 150 million children under age five worldwide, according to the World Health Organization. Existing therapeutic foods were developed to increase the amount of key nutrients children consume. Malnourished children who receive these foods are less likely to die, but other consequences of malnutrition have remained largely unresponsive to treatment, including stunted growth, impaired immunity, and reduced cognitive function. Disruption of the normal gut microbiota is common in malnutrition, and recent research suggests that without fixing this “immature” microbiota, even children given supplementary food may not be able to thrive.
The team transplanted immature microbial communities from malnourished children, and normally maturing microbial communities from healthy children, into sterile mice. The results revealed that immature communities were associated with reduced weight gain, defective bone development plus abnormal metabolic and immune functions in the recipient animals. These findings provided early evidence that failure to form a normal microbial community may be a cause rather than an effect of malnutrition.
“A longer and larger clinical trial is currently underway at two sites in Bangladesh to see if the new microbiome-directed complementary food has sustained benefits,” Ahmed said. “This trial includes children with moderate malnutrition as well as children with severe malnutrition treated with conventional therapy but left with incompletely repaired microbiomes, stunting and various other growth impairments.”
Added Michael J. Barratt, PhD, an assistant professor of pathology and immunology and executive director of the Center for Gut Microbiome and Nutrition Research at Washington University: “It is possible that some children may have gut microbial communities so damaged that a food-based intervention alone won’t be sufficient. So our Washington University and International Centre for Diarrhoeal Disease Research team is interested in studying the possibility of giving the specific beneficial organisms—or even the beneficial products those microbes make, as we become more knowledgeable about what those are—in combination with a microbiome-directed complementary food. That could be a second line of defense. Our studies also present the possibility of monitoring development of gut microbial communities and catching deviations from normal development earlier in life, giving us opportunities for prevention.”
Gordon emphasized that their efforts designed to repair the perturbed microbial communities of malnourished children hold the promise of revealing more informed guidelines for feeding children in the first several years of life so that they can develop healthy microbiomes. “We need to be effective stewards of the precious microbial resources of our children,” he said. “If we are, the effects may be long-lived and herald a new dimension to preventive medicine—one that starts with their developing microbiomes.”