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 (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.
['Wang|Yurong|Y|', 'Sun|Lie|L|', 'Chen|Shanwen|S|', 'Guo|Shihao|S|', 'Yue|Taohua|T|', 'Hou|Qisheng|Q|', 'Feng|Mei|M|', 'Xu|Hao|H|', 'Liu|Yucun|Y|', 'Wang|Pengyuan|P|', 'Pan|Yisheng|Y|']
D000818:Animals D018938:Caco-2 Cells D062445:Claudin-1 D003967:Diarrhea D064806:Dysbiosis D004926:Escherichia coli D005767:Gastrointestinal Diseases D000069196:Gastrointestinal Microbiome D006801:Humans D007410:Intestinal Diseases D007413:Intestinal Mucosa D007422:Intestines D000077146:Irinotecan D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D019936:Probiotics D062725:Tight Junction Proteins
EcN Irinotecan Tight junction Gut microbiota Claudin-1 Chemotherapy