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

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

  • Life Sci. 2019 Aug 15;231:116529. doi: 10.1016/j.lfs.2019.06.004.
Yurong Wang 1 Lie Sun 1 Shanwen Chen 1 Shihao Guo 1 Taohua Yue 1 Qisheng Hou 1 Mei Feng 1 Hao Xu 1 Yucun Liu 1 Pengyuan Wang 1 Yisheng Pan 2
Affiliations

Affiliations

  • 1 Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
  • 2 Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China. Electronic address: [email protected].
Abstract

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 (EcNsup) 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, EcNsup ameliorated the decreased TER and increased FD-4 flux elicited by SN-38. Moreover, EcNsup 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.

Keywords

Chemotherapy; Claudin-1; EcN; Gut microbiota; Irinotecan; Tight junction.

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