One gut microbiota, Fusobacterium nucleatum aggravates Neonatal necrotizing enterocolitis by induction of IRF5 expression through lncRNA ENO1-IT1/miR-22-3p axis.

Abstract

We explored the effects of Fusobacterium nucleatum (F. nucleatum) in Neonatal necrotizing enterocolitis (NEC) and its possible mechanism. Patients with Neonatal NEC and normal healthy volunteers were collected for this study. Neonatal mice were administered with LPS and then exposed to hypoxia as a mice model of NEC. THP-1 cells were stimulated with LPS as an in vitro model of NEC. We have demonstrated F. nucleatum abundance correlated with patients with Neonatal NEC or mice with Neonatal NEC. Furthermore, F. nucleatum stimulated colitis and increased inflammation in mice and in vitro models. LncRNA ENO1-IT1 was an important target for F. nucleatum in NEC-inflammation. MiR-22-3p was a target gene of F. nucleatum in NEC via LncRNA ENO1-IT1. Next, IRF5 was a target gene of miR-22-3p in the function of F. nucleatum in NEC via LncRNA ENO1-IT1. Silencing IRF5 or over-expressing miR-22-3p relieved the role of lncRNA ENO1-IT1 on inflammation in NEC via CD206 and CD86 expression. Taken together, these results demonstrate that F. nucleatum is mechanically, biologically and clinically connected to NEC. LncRNA ENO1-IT1 may be important targets for F. nucleatum in NEC-inflammation, and a meaningful in treating patients with Neonatal NEC with elevated F. nucleatum.