In a trio of coordinated papers recently published in Science and Cell, researchers have shown strong evidence that the makeup of a young child’s gut microbiome could have significant influence on their susceptibility to malnutrition.
Malnutrition affects almost 800 million people a year, and is the leading cause of death for children under 5 years old. While a simple lack of food is a common reason for malnutrition, it can also be caused by consuming foods that lack significant nutrients to sustain growth and development.
With this in mind the first team of researchers, led by Jeffrey Gordon from Washington University’s School of Medicine, implanted germ-free mice with bacteria taken from malnourished and healthy children from Malawi. As expected, the microbes from healthy children resulted in no growth abnormalities, whereas mice given microbes from the malnourished children resulted in stunted growth and bone malformations.
In their Science paper, Gordon and colleagues sought to determine if the microbes caused the malnutrition, or if the lack of food affected the children’s microbiome. After implantation, the mice were all fed a Malawi diet corresponding to malnutrition. Those mice with “healthy” microbes grew bigger and were less diseased than those mice receiving “malnourished” microbes. When microbes from healthy children were given to mice with microbes from malnourished children, the healthy microbes outcompeted the malnourished microbes and reversed the growth abnormalities in the mice.
In the Cell paper the group wanted to see if components in mother’s breast milk, which is often the first outside food given to babies, would affect risk of malnutrition. The researchers found that malnourished Malawian children were more often born to mothers lacking sialylated oligosaccharides in their breast milk, and when germ-free mice were fed milk without sialic acid they had stunted growth. Based on these two papers, the researchers concluded that malnutrition begins with microbial digestion of sialic acid(s) from mother’s breast milk, which can be converted by the child’s microbiome to an as-yet-to-be-determined growth factor that affects development of the child and further microbial growth.
In a related but separate Science paper, a group led by François Leulier from the École Normale Supérieure de Lyon in France showed that secondary hormone signaling during infanthood can affect the microbiome and lead to malnutrition. The group showed that the presence or absence of insulin-like growth factor (IGF), a secondary hormone derived from primary growth hormone (GH) signaling in the somatotropic axis, directly determines whether mice developed a malnourished phenotype. Further, they proved that strains of Lactobacilli can protect against this malnutrition phenotype, as they do not need IGF to promote growth functions of the somatotropic axis; in malnourished children, Lactobacilli species are often absent.
Taken together, these studies show a significant impact of malnutrition on infant microbe composition and subsequent human growth. Both groups concluded in their papers that therapies targeting these microbes, such as exogenous sialic acid supplementation or colonization with Lactobacilli species in malnourished children, could alleviate many of the symptoms of malnutrition. These therapies would also be inexpensive and easy to administer, two crucial aspects for these impoverished communities.
Edward Marks is a PhD student at the University of Delaware. His research involves the healing of myocardial tissue after major cardiac events using nanomedicine techniques, with the goal of pushing any advancement directly into the clinic. Edward received his BS from Rutgers University and Masters from the University of Delaware.