A clinical trial reported in 2021 and conducted by a team of researchers from Washington University School of Medicine in St. Louis and the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh, showed that a newly designed therapeutic food aimed at repairing malnourished children’s underdeveloped gut microbiomes was superior to a widely used standard therapeutic food.
Now, another study from the same research team at Washington University School of Medicine has identified key, naturally occurring biochemical components of this new therapeutic food and the important bacterial strains that process these components. The study suggests that identifying these components and the key growth-promoting gut bacterial strains that function as their therapeutic targets can help guide treatment with the current food formulation and could enable creation of new, more effective formulations in the future.
The study, led by Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor at Washington University, is published Dec. 13 in Nature.
“We have identified bioactive elements of a microbiome-directed food,” said Gordon, who is also director of the Edison Family Center for Genome Sciences & Systems Biology at the School of Medicine. “These are naturally occurring carbohydrate structures that could, in theory, be recovered in large quantities from the byproduct streams of food manufacturing and be used to produce prebiotics. We also have identified the microbes that process these food components, and in theory, there is potential for the organisms themselves to be part of a therapeutic intervention in children completely lacking these beneficial gut microbes.”
Building on this work, the World Health Organization together with the Bill & Melinda Gates Foundation is supporting a large, multisite clinical trial investigating this new therapeutic food — called MDCF-2, or microbiome-directed complementary food. The trial, which is in its early stages, aims to enroll about 6,500 malnourished children, ages 6 months to 2 years, living in Africa and Southeast Asia.
Malnutrition is a leading cause of death in children under age 5, and nearly 150 million children under this age suffer from stunted growth, according to the World Health Organization and the United Nations Children’s Fund. Treatment with traditional therapeutic foods reduces deaths, but it does not substantially improve other long-term effects of malnutrition, including problems with metabolism, bone growth, immune function and brain development.
“Our work has demonstrated that a healthy microbial community in the gut is necessary for healthy growth,” Gordon said. “Development of the gut microbial community in the first two years of life needs to be in sync with the development of the rest of the body, the other organ systems. When this microbial community is incompletely formed, simply giving more calories won’t repair it. We are seeking specific food components that nurture healthy gut microbial communities in hopes of repairing the gut microbial community that has become dysfunctional in children with malnutrition.”
The researchers, including co-first authors Matthew C. Hibberd, PhD, an assistant professor of pathology and immunology, and Daniel M. Webber, MD, PhD, an instructor in pathology and immunology, found that strains of the bacteria Prevotella copri were positively associated with increased growth in the children. These organisms showed increases in the activities of metabolic pathways that use beneficial bioactive carbohydrate structures present in the MDCF-2 therapeutic food. Compared with children receiving the traditional therapeutic food, those receiving MDCF-2 showed higher blood levels of certain proteins that support musculoskeletal growth and neurodevelopment as well as lower levels of proteins involved with inflammation — indicating that the effects of microbiome repair extend well beyond the walls of the gut.