Researchers compare the gut viromes of Malawian children with severe acute malnutrition

(Medical Xpress)—Malnutrition is a leading cause of child mortality, and evidence is accumulating that it is not solely attributable to food insecurity. Maternal behaviors, environmental factors, and a host of complex developmental variables can contribute to the onset of severe acute malnutrition (SAM). Recently, an international group of researchers conducted a study of the gut DNA viromes of twins in Malawi that were discordant for severe acute malnutrition in order to define a familial risk for childhood malnutrition and to provide a viral dimension to the body of knowledge about the gut microbiome. They have reported their findings in the Proceedings of the National Academy of Science.

The bacterial population of the human gut microbiota goes through postnatal developmental stages that researchers have characterized in pediatric studies. During the first two to three years of life, the microbiome in healthy infants develops from an immature state to a recognizable adult stage. In severe acute malnutrition, normal postnatal maturation of the microbiota is disrupted. Children with SAM in Malawi and Bangladesh have gut microbiota that appear to have the characteristics of those of much younger individuals.

Significantly, this immaturity is unaffected by the current peanut-based ready-to-use therapeutic food (RUTF) interventions, even when treated children reach normal weight. Such therapy has dramatically reduced mortality, but fails to ameliorate long-term health problems associated with childhood malnutrition, and the development of the gut microbiome may be a contributing factor.

In their study, the researchers found that discordance for malnutrition among 317 twin pairs from five rural Malawian villages was surprisingly high during the first three years of life. They compared the gut viromes of these twins with those of twins concordant for healthy status in order to characterize normal versus postnatal acquisition of the microbiota's viral component.

Previous studies have yielded models of age-discriminatory bacterial strains that serve as a signature of normal developmental biology; the time-dependent changes in the gut microbiota are similar between unrelated individuals living in different geographic areas, which suggests a set of developmental rules that have not yet been established.

The current study adds to this body of knowledge by contributing a developmental viral component. The researchers quantified gut virome abundances as a function of individual, twin-pair, age, health, and family variables and yielded a set of age-discriminatory phage and eukaryotic gut viruses.

Rather than providing a direct therapeutic approach to malnutrition, the study seeks to enlarge the existing picture of the microbiomes of malnourished and healthy people. For instance, by establishing a baseline for microbiome health, it may someday be possible to transplant healthy gut microbes into malnourished individuals receiving RUTF therapy in order to improve their long-term health.

However, the authors observe that "viral-bacterial dynamics in vivo are complex; the correlations between phage and bacterial strain abundances are not always obvious and involve negative correlations shifted in time as a result of a predator-prey dynamic, whereas prophages have linear positive correlations. As a consequence, answering this question promises to be challenging."