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<i>Bacteroides fragilis</i> is a commonly investigated commensal bacterium for its protective role in host diseases. Here, we aimed to develop a reproducible antibiotic-based model for conditioning the gut microbiota and engrafting <i>B. fragilis</i> into a conventional murine host. Initially, we selected different combinations of antibiotics, including metronidazole, imipenem, and clindamycin, and investigated their efficacy in depleting the mouse <i>Bacteroides</i> population. We performed 16S rRNA sequencing of DNA isolated from fecal samples at different time points. The α-diversity was similar in mice treated with metronidazole (MET) and differed only at weeks 1 (<i>p</i> = 0.001) and 3 (<i>p</i> = 0.009) during metronidazole/imipenem (MI) treatment. <i>Bacteroides</i> compositions, during the MET and MI exposures, were similar to the pre-antibiotic exposure states. Clindamycin supplementation added to MET or MI regimens eliminated the <i>Bacteroides</i> population. We next repeated metronidazole/clindamycin (MC) treatment in two additional independent experiments, followed by a <i>B. fragilis</i> transplant. MC consistently and reproducibly eliminated the <i>Bacteroides</i> population. The depleted <i>Bacteroides</i> did not recover in a convalescence period of six weeks post-MC treatment. Finally, <i>B. fragilis</i> was enriched for ten days following engraftment into <i>Bacteroides</i>-depleted mice. Our model has potential use in gut microbiota studies that selectively investigate <i>Bacteroides’</i> role in diseases of interest.