Brief background of the proposal and its relevance to the CDI’s objectives
Necrotizing enterocolitis (NEC) is one of the most critical challenges encountered by infants born preterm. NEC, an inflammatory bowel necrosis that is highly fatal, is the leading cause of death for premature infants after the second week of life. So far, no preventive strategy has meaningfully reduced the rate of NEC. Recent data suggest that gut dysbiosis precedes NEC onset, with an excess of Gammaproteobacteria and underrepresentation of strict anaerobes. Although sequencing reveals bacterial composition and gene content in the gut, the functional capacities and metabolism of the host and the gut can only be hypothesized. A preliminary untargeted metabolic analysis identified several host lipids as being differentially represented in cases versus controls, before NEC ensues. The goal of this project is to pursue these findings.
Proposed specific aims
· Define alterations in host lipids prior to NEC onset by targeted mass spectrometry.
· Define the role host lipids play in NEC-related gut injury.
Potential impact on child health
These findings could be used to identify at-risk patients to provide targeted care and prevent the onset of this devastating disorder, and to avert its life-long consequences.