Germ-free and Antibiotic-treated Mice are Highly Susceptible to Epithelial Injury in DSS Colitis
Metadatos
Mostrar el registro completo del ítemAutor
Hernández Chirlaque, Cristina; Aranda, Carlos J.; Ocón, Borja; Capitán Cañadas, Fermín; Ortega González, Mercedes; Suárez Ortega, María Dolores; Zarzuelo Zurita, Antonio; Sánchez De Medina López-Huertas, Fermín; Martínez Augustín, María OlgaEditorial
Oxford Univ Press
Materia
Germ-free Mucosal Barrier function Microbiota
Fecha
2016-04-26Referencia bibliográfica
Hernández-Chirlaque, C., Aranda, C. J., Ocón, B., Capitán-Cañadas, F., Ortega-González, M., Carrero, J. J., ... & Martínez-Augustin, O. (2016). Germ-free and antibiotic-treated mice are highly susceptible to epithelial injury in DSS colitis. Journal of Crohn's and Colitis, 10(11), 1324-1335. [doi:10.1093/ecco-jcc/jjw096]
Patrocinador
Ministerio de Economía y Competividad [Spain]; European Union (EU) SAF2008-01432 AGL2008-04332 SAF2011-22922 SAF2011-22812 BFU2014-57736-P AGL2014-58883-R; Fundación Ramón Areces [Spain]; Junta de Andalucía CTS164 CTS235 CTS6736; Ministerio de Educación [Spain]; Swedish Research Council; Instituto de Salud Carlos III; Spanish Government; European Union (EU) BFU2007-30688-E/BFIResumen
Background and Aims: Intestinal microbiota is required to maintain immune homeostasis and
intestinal barrier function. At the same time, intraluminal bacteria are considered to be involved
in inflammatory bowel disease and are required for colitis induction in animal models, with the
possible exception of dextran sulphate sodium [DSS] colitis. This study was carried out to ascertain
the mechanism underlying the induction of colitis by DSS in the absence of bacteria.
Methods: Conventional and germ-free [GF] Naval Medical Research Institute [NMRI] mice were
used, plus conventional mice treated with an antibiotic cocktail to deplete the intestinal microbiota
[‘pseudo-GF’ or PGF mice]. The differential response to DSS was assessed.
Results: Conventional mice developed DSS-induced colitis normally, whereas GF mice showed
only minimal inflammation [no colonic thickening, lower myeloperoxidase activity, IL-6, IL-17, TNF-
α, and IFN-γ secretion by splenocytes and mesenteric cell cultures, etc.]. However, these mice
suffered enhanced haemorrhage, epithelial injury and mortality as a consequence of a weakened
intestinal barrier, as shown by lower occludin, claudin 4, TFF3, MUC3, and IL-22. In contrast, PGF
mice had a relatively normal, albeit attenuated, inflammatory response, but were less prone to
haemorrhage and epithelial injury than GF mice. This was correlated with an increased expression
of IL-10 and Foxp3 and preservation barrier-related markers.
Conclusions: We conclude that enteric bacteria are essential for the development of normal DSSinduced
colitis. The absence of microbiota reduces DSS colonic inflammation dramatically but it also
impairs barrier function, whereas subtotal microbiota depletion has intermediate effects at both levels.