Early blood transcriptomic markers of necrotizing enterocolitis in preterm piglets

Necrotizing enterocolitis (NEC), a severe gut disorder in preterm infants, is difficult to predict due to poor specificity and sensitivity of clinical signs and biomarkers. Using preterm piglets as a model, we hypothesized that early development of NEC affects blood gene expression, potentially related to early systemic immune responses. In this animal model, variable severity of gut NEC lesions were detected in 5d-old piglets with limited clinical signs. NEC (n=20) and control piglets (CON, n=19) were analyzed for whole blood transcriptome, revealing 344 differentially expressed genes (DEGs) between NEC and CON piglets. Co-expression network analyses and qPCR suggested AOAH, FKBP5, PAK2 as three NEC-specific genes associated with severe gut lesions. These results suggest that whole blood gene expressions are affected in preterm piglets when clinical symptoms of NEC are minimal. Blood transcriptome may be a novel tool to identify early biomarkers of NEC. A retrospective analysis of clinical data was performed on 129 formula fed piglets that had NEC diagnosis at necropsy on day 5. Subgroups of NEC (n=20) and control piglets (CON, n=19) were analyzed for whole blood transcriptome. Key genes were validated in whole blood and dried blood spots by qPCR.