Maternally acquired genotoxic Escherichia coil alters offspring's intestinal homeostasis

被引:74
作者
Payros, Delphine [1 ,2 ,3 ,4 ,5 ]
Secher, Thomas [1 ,2 ,3 ,4 ]
Boury, Michele [1 ,2 ,3 ,4 ]
Brehin, Camille [1 ,2 ,3 ,4 ,6 ]
Menard, Sandrine [5 ]
Salvador-Cartier, Christel [5 ]
Cuevas-Ramos, Gabriel [1 ,2 ,3 ,4 ]
Watrin, Claude [1 ,2 ,3 ,4 ]
Marcq, Ingrid [7 ]
Nougayrede, Jean-Philippe [1 ,2 ,3 ,4 ]
Dubois, Damien [1 ,2 ,3 ,4 ,6 ]
Bedu, Antoine [8 ]
Garnier, Fabien [9 ,10 ]
Clermont, Olivier [11 ]
Denamur, Erick [11 ]
Plaisancie, Pascale [12 ]
Theodorou, Vassilia [5 ]
Fioramonti, Jean [5 ]
Olier, Maiwenn [1 ,2 ,3 ,4 ,5 ]
Oswald, Eric [1 ,2 ,3 ,4 ,6 ]
机构
[1] INRA, USC 1360, Toulouse, France
[2] INSERM, UMR1043, Toulouse, France
[3] CNRS, UMR5282, Toulouse, France
[4] Univ Toulouse, UPS, Toulouse, France
[5] INRA, UMR Toxalim, ENVT 1331, Neurogastroenterol & Nutr, Toulouse, France
[6] CHU Toulouse, Hop Purpan, Serv Bacteriol Hyg, Toulouse, France
[7] Univ Picardie Jules Verne, EA 4666, UFR Med Amiens, Amiens, France
[8] CHU Limoges, Serv Pediat, Limoges, France
[9] INSERM, U1092, Limoges, France
[10] Univ Limoges, UMR S1092, Limoges, France
[11] Univ Paris Diderot, PRES Sorbonne Cite, Inserm UMR S 722, Paris, France
[12] INRA, USC 1235, Inserm U1060, CarMeN Lab, Villeurbanne, France
关键词
Escherichia coli; colibactin; genotoxicity; neonate; gut; epithelial proliferation; epithelial differentiation; intestinal barrier;
D O I
10.4161/gmic.28932
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coil strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coil from mothers to neonates. Genotoxic and non-genotoxic E. con strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coil strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. con strains acquired at birth for gut homeostasis at adulthood.
引用
收藏
页码:313 / 325
页数:13
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