title: Antimicrobial growth promoters modulate host responses in mice with a defined intestinal microbiota.
abstract: Antibiotics can promote growth in livestock (antimicrobial growth promoters, AGPs), however lack of knowledge regarding mechanisms has hampered the development of effective non-antibiotic alternatives. Antibiotics affect eukaryotic cells at therapeutic concentrations, yet effects of AGPs on host physiology are relatively understudied, partially due to the complexity of host-microorganism interactions within the gastrointestinal tract. To determine the direct effects of AGPs on the host, we generated Altered Schaedler Flora (ASF) mice, and administered chlortetracycline (CTC) and tylosin phosphate (TYL) in feed. Mice were challenged with Citrobacter rodentium to determine how AGPs alter host responses to physiological stress. Although CTC and TYL had inconsistent effects on the ASF taxa, AGPs protected mice from weight loss following C. rodentium inoculation. Mice treated with either CTC or TYL had lower expression of βd1 and Il17a in the intestine and had a robust induction of Il17a and Il10. Furthermore, AGP administration resulted in a lower hepatic expression of acute phase proteins (Saa1, Hp, and Cp) in liver tissue, and ameliorated C. rodentium-induced reductions in the expression of genes involved in lipogenesis (Hmgcl and Fabp1). Collectively, this indicates that AGPs directly affect host physiology, and highlights important considerations in the development of non-antibiotic alternatives.
authors.affiliation: Agriculture and Agri-Food Canada, 5403-1st Avenue S, Lethbridge, AB, Canada.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Brown
authors.affiliation: Agriculture and Agri-Food Canada, 5403-1st Avenue S, Lethbridge, AB, Canada.|Department of Agricultural Food and Nutritional Science, University of Alberta, 410 Agriculture/Forestry Centre, Edmonton, AB, Canada.
authors.forename: Sarah J M
authors.initials: SJ
authors.lastname: Zaytsoff
authors.affiliation: Department of Agricultural Food and Nutritional Science, University of Alberta, 410 Agriculture/Forestry Centre, Edmonton, AB, Canada.
authors.forename: Richard R E
authors.initials: RR
authors.lastname: Uwiera
authors.affiliation: Agriculture and Agri-Food Canada, 5403-1st Avenue S, Lethbridge, AB, Canada.
authors.forename: G Douglas
authors.initials: GD
authors.lastname: Inglis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D002751:Chlortetracycline / Q000008:administration & dosage; D044082:Citrobacter rodentium / Q000187:drug effects / Q000472:pathogenicity; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects* / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics*; D058751:Livestock / Q000382:microbiology; D051379:Mice; D015645:Tylosin / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; C098680:Il17a protein, mouse; D020381:Interleukin-17; D002751:Chlortetracycline; D015645:Tylosin