Human Flora Associated (HFA) Mice: Effect of Selected Antimicrobials on the Human Intestinal Microflora

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Guyomard, Agnés (2011)
  • Publisher: Microbial Ecology in Health and Disease
  • Journal: Microbial Ecology in Health and Disease (issn: 1651-2235, eissn: 1651-2235)
  • Related identifiers: doi: 10.3402/mehd.v12i1.8048

The objectives of the research were to evaluate the effects of therapeutic and residual doses of tetracycline, neomycin and ciprofloxacin on the human intestinal flora using the human flora associated (HFA) mice model. Preliminary (in vitro) and definitive (in vivo) studies were performed with each drug. The preliminary studies included growth inhibitory activity of the antimicrobials against target human colonic bacterial species to select the dose to be added to the media for identifying the resistant aerobic and anaerobic bacteria in the in vivo studies. In addition, the stability of the antimicrobial substance was assessed in the drinking water to be given to mice in the in vivo studies. When possible, fecal antibiotic levels were measured during the treatment period. In the in vivo studies, germ-free mice inoculated with a dilution of pooled feces from selected donors received residual, medium or therapeutic doses of the antibiotics. The evolution of microbiological endpoints (total and resistant selected bacteria) and metabolic activity parameters [pH, bacterial proteins, enzyme activities, short-chain fatty acids (SCFA) and cellular fatty acids (CFA)] of the fecal microflora were compared in the treatment groups before, during and after drug exposure. The effect of the antibiotics on the colonization resistance properties of the intestinal flora was assessed by recording the kinetic of excretion of Salmonella in the treated animals after oral challenge. The risk of possible cross-contamination between animals located in the same isolator was studied by including a control cage in each treatment isolator and evaluating the most sensitive microbiological endpoints.
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