Stunted growth is a condition in which children have a short height for their age as a result of chronic or recurrent malnutrition. Affecting millions of children worldwide and often associated with environmental enteric dysfunction (EED), stunted growth can lead to increased morbidity and mortality, loss of physical growth potential, impaired neurodevelopmental and cognitive function, and increased risk of chronic disease in adulthood.
Recent studies of the microbiome of stunted children have found that small intestinal bacterial overgrowth (SIBO) is extremely common, affecting more than 80% of stunted cases. SIBO is often characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation, and the replacement of classical small intestinal strains, causing a microbial contribution to stunting through an imbalance in the microbiome.
Our goal is to selectively inhibit strains associated with stunting using compounds while preserving the commensal gut microbiota. To achieve this, a systematic in vitro high-throughput screening method was used to identify compounds that selectively inhibit enteric pathogens and oral bacteria associated with stunting while sparing gut commensals. Clinical isolates from stunted children were identified using a MALDI-TOF MS library method, which allows rapid and cost-effective identification of human commensal gut bacteria. The most promising compound candidates were then tested for selective inhibition in clinical isolates from stunted children, as well as in synthetic and patient stool bacterial communities. We are currently testing the most promising drug candidates in vivo in gnotobiotic mice models colonized with either a synthetic community associated with stunting or stool-derived communities from stunted children.
Restoring a healthy microbiome balance is expected to have anti-inflammatory effects, which in turn could alleviate the symptoms of stunting and positively impact children's health and development.