non-therapeutic administration of a model antimicrobial growth promoter modulates intestinal immune responses非治疗管理模型的抗生素生长促进剂调节肠道免疫反应.pdfVIP

Costa et al. Gut Pathogens 2011, 3:14 /content/3/1/14 RESEARCH Open Access Non-therapeutic administration of a model antimicrobial growth promoter modulates intestinal immune responses 1,2 3 1 2 1* Estela Costa , Richard RE Uwiera , John P Kastelic , L Brent Selinger and G Douglas Inglis Abstract Background: The development of efficacious alternatives to antimicrobial growth promoters (AGP) in livestock production is an urgent issue, but is hampered by a lack of knowledge regarding the mode of action of AGP. The belief that AGP modulate the intestinal microbiota has become prominent in the literature; however, there is a lack of experimental evidence to support this hypothesis. Using a chlortetracycline-murine-Citrobacter rodentium model, the ability of AGP to modulate the intestinal immune system in mammals was investigated. Results: C. rodentium was transformed with the tetracycline resistance gene, tetO, and continuous oral administration of a non-therapeutic dose of chlortetracycline to mice did not affect densities of C. rodentium CFU in feces throughout the experiment or associated with mucosal surfaces in the colon (i.e. at peak and late infection). However, chlortetracycline regulated transcription levels of Th1 and Th17 inflammatory cytokines in a temporal manner in C. rodentium-inoculated mice, and ameliorated weight loss associated with infection. In mice inoculated with C. rodentium, those that received chlortetracycline had less pathologic changes in the distal colon than mice not administered CTC (i.e. relative to untreated mice). Furthermore, chlortetracycline administration at a non-therapeutic dose did not impart either prominent or consistent effects on the colonic microbiota.