Scientists who first established a link between obesity and the trillions of friendly microbes that live in the intestine now are investigating whether the organisms can contribute to the converse: severe malnutrition.
School of Medicine researchers led by microbiologist Jeffrey Gordon, M.D., the Dr. Robert J. Glaser Distinguished University Professor, will study whether severely malnourished infants living in Malawi and Bangladesh have a different mix of intestinal microbes than healthy infants in the same areas and whether those microbes might account for their illness. This three-year, $5.5 million project is funded by the Bill & Melinda Gates Foundation.
“This work is designed to understand the complex interplay among a child’s diet and his or her gut microbial community, immune system and human genome in the development of the most severe forms of malnutrition, kwashiorkor and marasmus,” said Gordon, who directs the University’s Center for Genome Sciences. “Investigating how gut microbes contribute to malnutrition could provide a framework for developing more effective ways to treat and prevent these devastating diseases.”
The research will focus on twins ages 6 months to 2 years in which one or both twins is severely malnourished and, as a comparison, healthy twins. Identical and fraternal twins are being studied because they have identical or similar genetic backgrounds, and they share the same early environment after birth.
Gordon is teaming with Mark Manary, M.D., the Helene B. Roberson Professor of Pediatrics, who has spent more than two decades in Malawi treating malnourished children. Manary also helped develop a calorie-dense, enriched peanut-butter mixture that can be fed to malnourished children and has helped many of them recover. Gordon and members of his group also are working with members of the world-renowned International Center for Diarrheal Disease Research in Dhaka, Bangladesh.
As part of the project, malnourished infants will be given a nutritionally enriched food supplement.
“We will monitor the collection of microbial species and genes in the gut before, during and after treatment with the supplement and determine whether the collection of gut microbes and genes undergoes a change as a result of treatment,” Gordon said. “If alterations in the gut community do occur with treatment, does its ‘new state’ persist after cessation of therapy, or does it gradually revert to a state where the children are still at risk of malnutrition?”
The researchers also will analyze the gut microbes of the twins’ mothers. A recent study by Gordon and his colleagues found that bacterial communities in the gut appear to be transmitted in a significant way from mothers to their offspring.
The grant is part of a nearly $30 million initiative by the Gates Foundation to fund research into the root causes of malnutrition in the developing world. As part of this project, the WUSTL investigators will join forces with scientists at the University of Virginia, who will characterize the human genomes of identical and fraternal twins enrolled in this study to determine whether there are alterations in their human genes that regulate nutrient transport and processing.
By applying new genomic methods and computational tools for mining the massive data that emanate from the Malawi and Bangladesh sites, Gordon, Manary and their team, which also includes colleagues at the University of Colorado at Boulder, hope to develop a new understanding of the basis for malnutrition and test their theories at other sites in the foundation’s global network.