An Archetypical Model for Engrafting Bacteroides fragilis into Conventional Mice Following Reproducible Antibiotic Conditioning of the Gut Microbiota

Abstract

Bacteroides fragilis 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 B. fragilis 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 Bacteroides 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 (p = 0.001) and 3 (p = 0.009) during metronidazole/imipenem (MI) treatment. Bacteroides 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 Bacteroides population. We next repeated metronidazole/clindamycin (MC) treatment in two additional independent experiments, followed by a B. fragilis transplant. MC consistently and reproducibly eliminated the Bacteroides population. The depleted Bacteroides did not recover in a convalescence period of six weeks post-MC treatment. Finally, B. fragilis was enriched for ten days following engraftment into Bacteroides-depleted mice. Our model has potential use in gut microbiota studies that selectively investigate Bacteroides’ role in diseases of interest.

The Causal Impact of the Gut Microbiota on Respiratory Tuberculosis Susceptibility

“…Emerging research has demonstrated that a variety of lung diseases, including cystic fibrosis, asthma, and COVID-19, are linked with dysregulation of the gut microbiota, acting as a potential contributory factor that impacts their onset and progression [3][4][5][6]. For TB, some animal experiments have indicated that the gut microbiota could affect the susceptibility to TB [7][8][9][10][11][12]. TB infection can be promoted by broadspectrum antibiotics through disrupting the gut microbiota [7][8][9][10], and direct oral administration of gut bacteria or fecal transplantation could reduce TB infection in mice [7,11,12].…”

“…For TB, some animal experiments have indicated that the gut microbiota could affect the susceptibility to TB [7][8][9][10][11][12]. TB infection can be promoted by broadspectrum antibiotics through disrupting the gut microbiota [7][8][9][10], and direct oral administration of gut bacteria or fecal transplantation could reduce TB infection in mice [7,11,12]. Only a few observational studies have explored the association between patients with TB and healthy individuals [13][14][15][16][17][18][19][20].…”