Microbiome-based Strategies for Biocontrol of Preterm Necrotizing Enterocolitis

Principal Investigators:
Hall, Lindsay, TUM

Deng, Li, TUM

Necrotising enterocolitis (NEC) is a serious condition affecting between 5-15% of preterm infants, and is associated with overgrowth of multi-drug resistant pathogenic microbiota members. There is a clear need for new treatment approaches that circumvent the threat of antimicrobial resistance, and (bacterio)phages represent an attractive therapeutic target. This new project will explore the main bacterial species that are associated with NEC through a combination of metagenomics, culturing and whole genome sequencing studies, as well as to define strain level relationships. Using cutting-edge phage isolation and characterisation approaches we will identify phage isolates and optimal phage combinations against the main NEC-causing pathogens, and delineate how phage(s) impact the wider preterm microbiota, including probiotic genera using model gut systems. Finally, after pre-screening a wide range of phage-pathogen combinations in the wax moth in vivo model, we will determine efficacy of key phage cocktails against NEC pathogens using clinically relevant pig models, and thus define optimal therapeutic products that could be tested in the clinic within the next funding phase.