Non-therapeutic administration of a model antimicrobial growth promoter modulates intestinal immune responses
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Date
2011
Authors
Costa, Estela
Uwiera, Richard R. E.
Kastelic, John P.
Selinger, L. Brent
Inglis, G. Douglas
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
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.
Conclusion: Data 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.
Description
Sherpa Romeo green journal: open access
Keywords
Antimicrobial growth promoters , AGP , Chlortetracycline , Citrobacter rodentium , Immunomodulation hypothesis
Citation
Costa, E., Uwiera, R.R.E., Kastelic, J.P., Selinger, L.B., & Inglis, G.D. (2011). Non-therapeutic adminstration of a model antimicrobial growth promoter modulates intestinal immune responses. Gut Pathogens, 3(14).doi:10.1186/1757-4749-3-14: