Gamma‐Glutamyl‐Cysteine Alleviates Inflammatory Bowel Disease by Suppressing the NF‐κB Pathway in Jejunum and Modulating the Gut Microbiota

This study aimed to reveal the molecular mechanism by which gamma‐glutamyl‐cysteine (γ‐EC) alleviates jejunal inflammation in inflammatory bowel disease (IBD) and whether it involves the NF‐κB pathway and the alterations in the gut microbiota. In this study, lipopolysaccharides (LPS)‐induced IBD mouse models and intestinal porcine epithelial cells from the jejunum (IPEC‐J2) were used to demonstrate the therapeutic effects of γ‐EC on intestinal barrier dysfunction in vivo and in vitro, respectively. Here, LPS‐induced IBD mice suggest that γ‐EC has the potential to modify jejunal intestinal barrier by enhancing the expressions of tight junction protein (ZO‐1, occludin, and claudin‐1) and decreasing the expressions of NF‐κB pathway‐associated protein (IKKα, IκBα, and p65). Further detection revealed that γ‐EC successfully increased the abundance of Akkermansia and enhanced the production of gut short‐chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Eventually, LPS‐treated IPEC‐J2 cells validated that γ‐EC upregulated the mRNA expressions of ZO‐1 and claudin‐1. These findings suggest that γ‐EC had the potential to mitigate IBD‐induced inflammation in jejunum by modulating the NF‐κB pathway, modulate the gut microbiota and SCFAs, and might be a therapeutic agent for intestinal inflammation related to IBD.