Grant: Travel Awards - Institute Community Support

Malnutrition is a leading cause of child mortality worldwide and has long-lasting health and socio-economic consequences. Currently available therapies are diet-based, with protein-rich supplements provided to malnourished children for short periods of time. Yet, post-therapy return to a malnourished state is common, highlighting the need for alternative approaches. The trillions of bacteria, viruses, and fungi found in the human gut, known as the gut microbiota, have important roles in human health, and disturbances to their establishment in early life can lead to a variety of health conditions. Studies have shown causal links between the gut microbiota and childhood malnutrition, with delayed microbiome development and higher prevalence of bacterial pathogens in malnourished children. Bacteriophages (phages), viruses infecting bacteria but causing no harm to the human host, are the most abundant members of the gut virome (viral fraction of gut microbiota). Previous work from our lab has shown that fecal virome transplants (FVT) from healthy children can shift the gut microbiome of malnourished children to a healthy state in vitro. We thus hypothesize that this approach can be used for improving clinical outcomes and restoring healthy gut microbiome development in malnutrition. To do this, I will first compete the validation of a humanized mouse model of intergenerational early life malnutrition. Then, I will proceed with FVTs from healthy donors to malnourished neonatal mice and evaluate their effects on restoring microbiome development and animal growth. Finally, I will compare the effects of a combination of FVTs & diet supplementation to each therapy alone to identify the most promising approach. Ultimately, we hope that the proposed novel phage-based therapy, combined with existing dietary interventions, will improve health outcomes for the almost 200 million children worldwide suffering from malnutrition.