Lactobacillus reuteri 100-23 transiently activates intestinal epithelial cells of mice that have a complex microbiota during early stages of colonization.
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.
Hoffmann
Micha
M
Chair for Biofunctionality, Nutrition and Food Research Center, Technische Universität München, 85350 Freising-Weihenstephan, Germany.
Rath
Eva
E
Hölzlwimmer
Gabriele
G
Quintanilla-Martinez
Leticia
L
Loach
Diane
D
Tannock
Gerald
G
Haller
Dirk
D
D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D020869:Gene Expression Profiling; D007413:Intestinal Mucosa / Q000166:cytology* / Q000382:microbiology; D052200:Limosilactobacillus reuteri / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger