Principal Investigator (PI)
The Foundation is providing £222,242 in support.
Nermin Akduman
The project would immensely benefit from the exceptional setting of the Tres Cantos Open Lab Foundation, allowing access to topnotch expertise in screening and drug development and connections to a network of experts in the EED field. Furthermore, an ‘Open Lab’ collaboration would offer a unique opportunity to conduct a pioneering and innovative study on microbiome modulating therapeutics with broader impact, as the presence of members of the oral microbiome at distant body sites is not restricted to EED alone but also typical for other inflammatory diseases including colorectal cancer and rheumatoid arthritis.
Environmental enteric dysfunction (EED) is a poorly understood inflammatory syndrome characterized by reduced absorptive capacity and barrier function in the small intestine. It is widespread among children in low-income countries and impairs child growth and development (stunting). Although various infectious agents have been suggested to cause EED, recent evidence supports the idea that a “decompartmentalization” of intrinsic throat microbes towards the small intestine combined with a depletion of beneficial butyrate-producing microbes sustains inflammatory conditions. Effective treatment strategies such as microbiome modulation to revert this imbalance are still missing. The overarching goal of this study is to identify lead compounds, drugs or drug/food combinations that modulate the gastrointestinal microbiome in stunted children towards a healthy microbial community. To this end, we propose screening for inhibitors of EED-related taxa from the oropharynx and for growth enhancers of protective microbes. This endeavor will profit from both, GSK’s compound libraries, expertise and screening platforms as well as from our recently established anaerobic high-throughput platform that is perfectly geared towards the needs of fastidious EED-related microbes. Promising candidates/combinations will be followed up in vitro with EED-mimetic microbial communities and in vivo using EED gnotobiotic mouse models. Successful microbiome modulators have tremendous potential to resolve EED’s inflammatory conditions with crucial impact on growth and development of young children around the world.