CLN Daily
This year’s Wallace H. Coulter Lectureship Awardee is Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences and Systems Biology at Washington University School of Medicine in St. Louis. Known as the “father of the microbiome,” Gordon has had an incredible career studying the symbiotic relationship between gut microbes and human development. A member of the National Academy of Sciences, he has been honored with many awards, including the Louisa Gross Horwitz Prize in 2017, the Copley Medal in 2018, the Balzan Prize in 2021, and the Dr. Paul Janssen Award for Biomedical Research earlier this year.
The principal focus of his laboratory is the role of the gut microbial community (microbiota) and the vast repository of genes (microbiome) in regulating the healthy growth of infants and children and in the pathogenesis of malnutrition. In yesterday’s opening plenary and award lecture, titled “Developing Microbiome-Directed Therapeutics for Treating Childhood Undernutrition,” Gordon described his team’s groundbreaking findings and exciting future directions for their work.
His interdisciplinary team had the following questions: Is there a definable “normal” for the development of a healthy gut microbial community? If so, is there a perturbation in development of this microbial “organ” in infants and children with undernutrition? If so, is this disturbance a cause or an effect of disease? These questions challenged the established narrative that the only requirement for treating malnutrition was sufficient calories. Answering them required translational research in an area of the world where the burden of undernutrition was profound, and where trusted health workers could conduct longitudinal studies of healthy and malnourished children with full support from their caregivers and communities.
Gordon teamed up with Dr. Tahmeed Ahmed, a long-standing collaborator in this research and executive director of the International Centre for Diarrhoeal Disease Research in Bangladesh. Ahmed says the number #1 problem for humankind is the 800 million people needlessly suffering from hunger.
The researchers began by defining “normal” gut development in healthy members of Bangladeshi birth cohorts, who were tracked at monthly intervals from birth through age 5. Then they identified metrics to define deviations from normal. This led to the revelation that children with undernutrition had immature microbial communities. These children appeared younger than expected based on their chronologic age.
The researchers created preclinical models to show that this microbial immaturity was causally related to disease. The same models were subsequently used to identify therapeutic targets in the microbial community and develop culturally acceptable, affordable, and scalable candidates for therapeutic intervention. Their preclinical development of so-called “microbiota-directed complementary food” formulations, or MDCFs, was followed by randomized controlled clinical studies in malnourished Bangladeshi children. Their lead MDCF produced superior weight gain and pronounced changes in the levels of proteins critical for healthy growth compared to standard, more calorically dense, therapeutic food formulations that were not designed to repair damaged microbiomes.
“These findings not only support the hypothesis that the gut microbial community is linked to healthy postnatal development,” said Gordon, “but they open the door to learning key lessons from microbiota repair. Namely, how do different components of the gut community act to regulate various aspects of growth of their human hosts?”
Gordon’s future work will include testing the durability and generalizability of MDCF treatments in children of different ages living in other parts of the world. A particular area of interest for lab medicine professionals, Gordon said, is “the development of affordable point-of-care diagnostics for determining the functional status of an infant’s and a child’s developing gut community. These tools will be required to stratify populations with disease prior to selecting the form of treatment—for example, food-based and/or next-generation probiotics—to define the efficacy of current and future therapies, and for developing effective, implementable strategies for ensuring healthy development of our children’s precious microbial resources.”