Rosmarinic acid alleviated intestinal barrier damage caused by Escherichia coli by regulating the gut microbiota and inhibiting the NF-κB signalling pathway in mice.

Abstract

Escherichia coli (E. coli) is a common zoonotic foodborne pathogen that poses a major threat to public health and economic development. Rosmarinic acid (RA) can inhibit intestinal inflammation; however, the protective effect of RA against the intestinal barrier damage induced by E. coli in mice and the underlying mechanism have not been elucidated. In this study, mice were orally administered with RA (20 mg kg^-1) by gavage for one week and then were intraperitoneally challenged with E. coli. Mouse colonic epithelial cells (MCECs) were pretreated with RA for 6 h and challenged with E. coli (MOI = 1000) for 3 h. The results revealed that RA alleviated E. coli-induced weight loss in mice; reduced the increase in the levels of TNF-α, IL-6 and IL-1β in the serum; alleviated the decrease in ZO-1 protein expression; and increased intestinal permeability by inhibiting the NF-κB signalling pathway both in vivo and in vitro. Moreover, RA relieved the increase in intestinal permeability, reversed the structural damage to the mouse gut microbiota caused by E. coli, and increased the abundance of beneficial bacteria, including Lachnospiraceae_NK4136_group. Additionally, RA lost its protective function against E. coli infection in a pseudosterile mouse model, suggesting that the protection induced by RA was dependent on the gut microbiota. In conclusion, these results indicate that RA alleviates E. coli-induced inflammatory damage to the intestinal barrier by inhibiting the NF-κB signalling pathway and maintaining gut microbiota homeostasis. These findings provide new ideas and foundations for the application of RA as protection against E. coli.