Intestinal metabolomics analysis reveals lysophosphatidylcholine is the key regulatory metabolite in mouse models of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a severe intestinal emergency in neonates. This study explored NEC-related biomarkers by metabolomics to provide new insights for the clinical therapy of NEC. A mouse NEC model was induced by lipopolysaccharide (LPS), hypoxia, and cold stress. Hematoxylin and eosin (H&E), Ki-67, and TUNEL staining were used to detect the pathological changes in mouse intestinal tissues; the intestinal mRNA expression levels of inflammatory-associated cytokines were detected using qRT-PCR. Intestinal content samples of NEC mice were analyzed by metabolomics. Lysophosphatidylcholine (15:0/0:0) (lysoPC) effects on NEC were explored in both in vivo and in vitro models. NEC mice showed significantly decreased body weight and survival rate, shortened intestinal length, and significant pathological changes. Moreover, in NEC mice, intestinal cell proliferation was reduced, apoptosis was increased, and IL-1β, IL-6, and TNF-α mRNA expressions dramatically increased while IL-10 mRNA expression was reduced. According to the metabolomics results, lysoPC level was significantly reduced in the intestinal contents of the NEC group. Supplementing lysoPC alleviated the pathological symptoms in NEC mice and reversed formate-induced injury in human intestinal epithelial cell line HIEC6. LysoPC supplementation alleviates the pathological symptoms of NEC mice, which is a promising novel option for the clinical treatment of NEC.