Lactobacillus GG regulates the Wnt/β-catenin pathway to reinforce intestinal barrier function and alleviate necrotizing enterocolitis

Abstract

Intestinal barrier function and intestinal flora imbalance lead to neonatal necrotizing enterocolitis (NEC). Lactobacillus rhamnosus GG (LGG) has been used to prevent or treat NEC in many animal models and clinical trials; however, its underlying action mechanism remains elucidated. Here, we observed intestinal stem cell (ISC) and intestinal barrier disruption in an NEC mouse model, characterized by reduced number of tight junctions (TJs) and expression of Lgr5, inhibition of ISC differentiation and the Wnt/β-catenin signaling pathway, and disturbance of the intestinal microbiota microenvironment. LGG oral administration in these mice re-established the intestinal flora, increased Wnt3a and Wnt7b levels in the small intestinal tissue, activated the Wnt/β-catenin signaling pathway, promoted ISC regeneration, reduced intestinal tumor necrosis factor-α and interleukin-6 levels, increased the number of TJs, and improved intestinal barrier function; NEC-induced intestinal injury was also reduced. Therefore, LGG administration can alleviate intestinal lesions by enhancing mucosal barrier function in NEC.

Keywords

• Lactobacillus
• Enterocolitis
• Tight junction
• Intestine
• Microbiota
• Wnt/β-catenin