Uncovering the biological basis of probiotic non-response in preterm gut health

This project aims to revolutionise probiotic therapy in preterm infants by uncovering why some individuals fail to respond to current treatments. Our unpublished data shows ‘non-response’ to treatment increases the risk of necrotising enterocolitis (NEC), an inflammatory bowel disease that represents a leading cause of death in preterm infants. The absence of specific maternal milk bioactive components and/or infant-related factors likely contribute. This will be investigated through three key aims: 1) Identify dietary and host factors associated with probiotic response, focusing on bioactive components in mother’s milk and infant immune/metabolic profiles. 2) Determine how diet and gut microbiome influence probiotic growth and function, using high- throughput microbial assays and metabolomics to test milk components and microbial interactions. 3) Mechanistically study host-microbe interactions using preterm intestinal organoids and a novel anaerobic co-culture system to assess how probiotics and milk components affect inflammation and gut health. The latter stages of the project will validate the results using other probiotics/cohorts and uncover the mechanisms using genetic manipulation approaches. This project leverages extensive biobank resources, advanced multi-omics, microbiology, and cutting-edge organoid models to generate fundamental discoveries. The outcomes will guide the development of personalised probiotic, prebiotic, and/or postbiotic therapies to improve preterm infant gut health.