Impact of Cross-Contamination Concentrations of Doxycycline Hyclate on the Microbial Ecosystem in an Ex Vivo Model of the Pig's Cecum

Aims: Cross-contamination of feed with antibiotics causes pigs to become unintentionally exposed to low concentrations of antibiotics. This study investigates the effect of residues of doxycycline hyclate (DOX) in an ex vivo model of the intestinal tract of pigs, focusing on the microbial community, microbial activity, and the enrichment of resistant bacteria and resistance genes.
Results: The effect of three concentrations DOX were tested; 1 and 4 mg/L correspond to the intestinal concentrations when pigs are fed a compound feed containing 3% of a therapeutic dose, and a reference concentration of 16 mg/L. These were continuously administered to a chemostat, simulating the microbial ecosystem of the pig cecum and inoculated with cecal content of organically grown pigs. The administration of even the lowest DOX concentration caused a significant decrease in bacterial activity, while the microbial community profile appeared to remain unaffected by any of the concentrations. A concentration of 1 mg/L DOX caused minor selection pressure for tetracycline-resistant Escherichia coli but no other groups enumerated with plate cultivation, while 4 mg/L induced major enrichment of tetracycline-resistant E. coli, Enterobacteriaceae and total anaerobes. High abundances of tet(Q), tet(M), tet(W), tet(O), and tet(B) were detected in the inoculum and also before antibiotic administration in the chemostat and did not significantly increase during administration of 1 and 4 mg/L DOX. Only 16 mg/L DOX caused minor enrichments.
Conclusions: Cross-contamination concentrations of doxycycline, as a result of cross-contamination, cause a selection pressure for resistant bacteria and negatively affect microbial activity.