PuSH - Publication Server of Helmholtz Zentrum München: Lactobacillus reuteri 100-23 transiently activates intestinal epithelial cells of mice that have a complex microbiota during early stages of colonization.

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Hoffmann, M.* ; Rath, E.* ; Hoelzlwimmer, G. ; Quintanilla-Martinez, L. ; Loach, D.* ; Tannock, G.* ; Haller, D.*

Lactobacillus reuteri 100-23 transiently activates intestinal epithelial cells of mice that have a complex microbiota during early stages of colonization.

J. Nutr. 138, 1684-1691 (2008)

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Monoassociations of germ-free animals with colitogenic and probiotic bacterial strains trigger intestinal epithelial cell (IEC) activation and host-derived feedback mechanisms. To characterize the impact of a single nonpathogenic bacterial strain on the intestinal epithelium in the presence of an established microbiota, we inoculated reconstituted Lacotobacillus-free (RLF) mice at 8 wk of age with Lactobacillus reuteri 100-23. Primary IEC from the small intestine of L. reuteri-inoculated and control RLF mice were isolated 2, 6, and 21 d after inoculation followed by gene expression analysis (real-time PCR; Affymetrix microarrays) as well as 2-dimensional-gel electrophoreses (2D SDS-PAGE) and peptide mass fingerprinting via matrix-assisted laser desorption/ionization time of flight MS. At d 6, gene expression of proinflammatory cytokines and chemokines including interleukin (IL)-1alpha, IL-6, interferon-gamma-inducible protein 10, and macrophage inflammatory protein 2 was transiently induced, whereas gene expression levels of regulatory proteins A20 and Toll-interacting protein decreased. In addition, 8 target proteins with changes in the steady-state protein expression levels were identified at d 2 and 6 of L. reuteri colonization. Consistent with the absence of histopathology, L. reuteri-induced activation of primary IEC returned to control levels by d 21 after inoculation of RLF mice. The capability of L. reuteri 100-23 to directly trigger epithelial cell activation was confirmed in small IEC cultures using the murine cell line Mode-K. These results clearly indicate that the intestinal epithelium is reactive toward environmental changes induced by the commensal bacterial strain L. reuteri even in the presence of an already-established microbiota. The induction of transient IEC activation may help to maintain mucosal homeostasis.

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