The administration of Escherichia coli Nissle 1917 ameliorates irinotecan-induced intestinal barrier dysfunction and gut microbial dysbiosis in mice.

AIMS

The present study investigated the effect of Escherichia coli Nissle 1917 (EcN) on irinotecan-induced intestinal barrier dysfunction and gut microbial dysbiosis in a mouse model and in the human colonic cells lines Caco-2.

MATERIALS AND METHODS

Male BALB/c mice received irinotecan intraperitoneal injection with or without EcN administration intragastrically. Body weight, diarrhea severity, intestinal permeability and histopathological analysis of ileum epithelia of mice from different groups were assessed. The expression and localization of tight junction proteins were examined using western blot and immunofluorescence. Gut microbiota structure and diversity were measured with 16 S rRNA sequencing. Caco-2 monolayers were incubated with EcN culture supernatant (EcN) or SN-38 and the monolayer barrier function was assessed by transepithelial electrical resistance (TER) and FITC-dextran 4000 Da (FD-4) flux.

KEY FINDINGS

Pretreatment with EcN significantly attenuated irinotecan-induced weight loss and diarrhea in mice. In addition, EcN inhibited the increased intestinal permeability and decreased Claudin-1 expression in irinotecan-treated mice. Furthermore, irinotecan treatment decreased the diversity of gut microbiota and increased the relative abundance of Proteobacteria compared to control group. EcN administration ameliorated the gut microbiota dysbiosis. In Caco-2 monolayers, EcN ameliorated the decreased TER and increased FD-4 flux elicited by SN-38. Moreover, EcN attenuated SN-38-induced altered localization and distribution of Claudin-1 in Caco-2 monolayers.

SIGNIFICANCE

Our results indicated that the administration of EcN protected against irinotecan-induced intestinal injury by regulating intestinal barrier function and gut microbiota.