Jeffrey Gordon, MD
Dr. Robert J. Glaser Distinguished University Professor, WashU Pathology & Immunology
- Phone: 314-362-7243
- Email: firstname.lastname@example.org
Gut microbiota immaturity in undernutrition and its effects on brain development
Childhood undernutrition can produce marked and, tragically, persistent cognitive abnormalities that are not rescued by current nutritional interventions. These abnormalities rob children of the opportunity to realize their full human potential and thus have immense ramifications for their own lives, their families, their communities, and their countries.
Applying machine learning methods to bacterial 16S rRNA datasets generated from fecal samples collected monthly (from 0-2 years) in members of birth cohorts living in India, Bangladesh, South Africa, Malawi, Peru, and Brazil, we developed generally applicable metrics [‘relative microbiota maturity’ and ‘microbiota-for-age Z score (MAZ)’] for defining normal assembly/maturation of the gut microbiota. Using these metrics, we have discovered that infants and children with undernutrition living in low-income countries have immature gut microbial communities: the normal postnatal program of microbial community (microbiota) development is perturbed producing a configuration that is immature compared to age-matched healthy individuals. Importantly, this immaturity is not durably rescued by current nutritional interventions.
Transplantation of gut microbiota from infants and children with healthy growth phenotypes and immature microbiota from infants/children with stunting and other manifestations of undernutrition to different groups of young (4 week old) germ-free mice fed diets representative of the microbiota donors established that microbiota immaturity is associated with transmissible growth, metabolic, immunologic, and bone abnormalities.
These results have led us to propose that healthy growth is dependent in part on proper functional development of the gut microbiota during the first 2 years of life and that children with undernutrition possess a persistent developmental abnormality of their gut’s microbial metabolic ‘organ’.
Work in the lab is currently focused on identifying food- and microbial-based interventions (that latter using a defined consortia of sequenced cultured members of the human gut microbiota) that can durably repair microbiota immaturity in our gnotobiotic mouse models. It is important to note that these preclinical models incorporate the very microbiota and diets of the populations we wish to treat; proof-of-concept, proof-of-mechanism tests conducted in these mice, and biomarkers identified from our analyses, can be used to identify and advance therapeutic leads for clinical proof-of-concept.