Abstract
BackgroundThe 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.ResultsC. 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.ConclusionData support the hypothesis that AGP function by modulating the intestinal immune system in mammals. This finding may facilitate the development of biorationale-based and efficacious alternatives to AGP.
Highlights
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 ‘immunomodulation hypothesis’ for AGP action is consistent with the growth-promotion effects observed when AGP is administered to animals possessing very disparate intestinal microbiota [12]
Non-therapeutic CTC administration modulated immune responses that were temporally related to C. rodentium infection, in accordance with the immunomodulation hypothesis of AGP action
Summary
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 AGP ban in the EU increased the therapeutic administration of antimicrobial agents [6], as well as the cost of animal production, and. The consistency of growth-promotion effects imparted by AGP on various animal species possessing highly dissimilar intestinal microbiota coupled with low concentrations at which AGP are administered (i.e. at doses less than the minimum inhibitory concentration for most pathogens) challenges the validity of the microbiota modulation hypothesis of AGP action [12]. The ‘immunomodulation hypothesis’ for AGP action is consistent with the growth-promotion effects observed when AGP is administered to animals possessing very disparate intestinal microbiota [12]. We formulated and tested the hypothesis that non-therapeutic concentrations of a model AGP administered orally to mammals will modulate enteric immune responses
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