Review of claudin proteins as potential biomarkers for necrotizing enterocolitis

Background Claudin proteins are a component of tight junctions found in cell-cell adhesion complexes. A central feature of necrotizing enterocolitis (NEC) is intestinal permeability, with changes to claudin proteins potentially contributing to intestinal instability, inflammation, and the progression of NEC. A current area of interest is the development of a novel, noninvasive biomarker for the detection of NEC in neonates at risk of developing this disease, in order to reduce morbidity and mortality through earlier intervention. Aims This review aims to explore the relevance of claudin proteins in the pathophysiology of NEC and their potential usefulness as a biomarker. Methods This review was conducted using the search terms "claudin" + "necrotizing enterocolitis", with 27 papers selected for review. Results Claudin proteins appear to have a role in the stability of the gut epithelium through the regulation of intestinal permeability, maturity, and inflammation. Formula feeding has been shown to promote inflammation and result in changes to claudin proteins, while breastfeeding and certain nutritional supplements lead to reduced inflammation and improved intestinal stability as demonstrated through changes to claudin protein expression. Preliminary studies in human neonates suggest that urinary claudin measurements may be used to predict the development of NEC. Conclusions Alterations to claudin proteins may reflect changes seen to intestinal permeability and inflammation in the context of NEC. Further research is necessary to understand the relevance of claudin proteins in the pathophysiology of NEC and their use as a biomarker.