Understanding the interaction between human milk oligosaccharides and the gut microbiome in preterm infant health and disease (360G-Wellcome-221745_Z_20_Z)

Necrotising enterocolitis (NEC) is a leading cause of death in babies born extremely preterm. NEC infants generally have increased gram-negative bacteria compared to matched controls, potentially resulting in an LPS-stimulated increase in TLR4 and inflammatory cytokines in the intestinal epithelium, ultimately leading to the breakdown of epithelial integrity and necrosis. My recent work has shown that human milk oligosaccharides (HMOs) promote the establishment of a protective microbiome in the infant gut, which is associated with reduced risk of NEC. This project will identify specific HMOs and bacteria that promote gut health and reduce NEC in preterm infants. The project will take advantage of a host-microbe model system I have recently developed. This will provide new insights into NEC pathogenesis, potentially leading to the development or refinement of therapeutics. I will achieve this by answering four critical questions: 1\. What specific HMOs and microbial species are associated with NEC or gut health? 2\. Do HMOs directly influence the epithelial integrity and inflammation observed in NEC? 3\. How do specific bacterial species interact with the preterm intestinal epithelium? 4\. Can a combination of HMO (prebiotic) and bacteria (probiotic) promote gut health and protect against NEC?