Gut Microbes Contribute to Severe Malnutrition in Young Malawian Twins
A study of young twin pairs in Malawi has shown that gut microbes may play an important role in causing severe malnutrition in children that persists in spite of nutritional interventions. Malnutrition is the top cause of child mortality in the world. Childhood malnutrition is common in some African countries like Malawi, where the diet is deficient in protein and the rate of infant mortality is one of the highest in the world. A type of severe malnutrition called kwashiorkor is thought to result from a combination of inadequate nutrient intake, particularly of protein, and other environmental factors. Although it is not fully understood why some children develop kwashiorkor, evidence from past studies has indicated a possible role in early development for the trillions of microbes that reside in the human gut. A group of researchers from the United States, Malawi, and the U.K. conducted a study of identical and fraternal twins born in Malawi to identify any links between gut microbes and severe malnutrition. They collected fecal samples every two weeks from pairs of twins with malnutrition under three years of age—before, during, and after they were given the standard treatment of ready-to-use therapeutic foods or supplements. In some cases, both twins became well-nourished; in others, one or both of the twins relapsed and again became malnourished after the nutritional therapy. The scientists concentrated on those pairs—similar in genetics, diet, and environment—in which one twin was well-nourished after treatment, while the other developed kwashiorkor. They analyzed the fecal samples to detect DNA from gut microbes, and found that different gut microbes were present in the well-nourished compared to the malnourished twin.
To see if the different microbes were affecting the nutritional state of the children, the scientists transplanted fecal matter from these twins into the guts of mice raised previously under sterile conditions. Then they fed the mice a diet based on foods eaten in Malawi prior to a two-week treatment with the ready-to-use therapeutic food, followed by resumption of the Malawian diet. The mice transplanted with the malnourished twins’ microbes lost much more weight than the mice transplanted with microbes from the well-nourished twins. Similar to the human twins, mice transplanted with the malnourished twins’ fecal samples harbored different types of bacteria, some of which have been linked to bowel disease, from those transplanted with material from the well-nourished twins. After the nutritional therapy, the mice with the malnourished twins’ microbes showed a shift to more healthy types of bacteria along with indicators of improved nutrition and metabolic function. However, after being put back on the Malawian diet for only four weeks, these indicators fell back to pre-treatment levels. This study’s finding—that the combination of dietary deficiency with a particular gut microbial profile causes severe malnutrition—has far-reaching implications for developing sustainable interventions for childhood malnutrition. For example, biomarkers of microbial metabolism may need to be taken into account for designing effective nutritional interventions in some individuals. These and other insights will be helpful in developing more effective approaches to treating and preventing the huge global challenge of severe malnutrition in children.