Clearance ofClostridioides difficilecolonization is associated with antibiotic-specific bacterial changes
Authors: Lesniak Nicholas A. , Schubert Alyxandria M. , Sinani Hamide , Schloss Patrick D. 
Published: November 2020

The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearingClostridioides difficilecolonization across different community perturbations. However, those bacteria alone have been unable to clearC. difficilecolonization. To elucidate the changes necessary to clear colonization, we compared differences in bacterial abundance between communities able and unable to clearC. difficilecolonization. We treated mice with titrated doses of antibiotics prior toC. difficilechallenge which resulted in no colonization, colonization and clearance, or persistent colonization. Previously, we observed that clindamycin-treated mice were susceptible to colonization but spontaneously clearedC. difficile.Therefore, we investigated whether other antibiotics would show the same result. We found reduced doses of cefoperazone and streptomycin permitted colonization and clearance ofC. difficile.Mice that cleared colonization had antibiotic-specific community changes and predicted interactions withC. difficile.Clindamycin treatment led to a bloom in populations related toEnterobacteriaceae.Clearance ofC. difficilewas concurrent with the reduction of those blooming populations and the restoration of community members related to thePorphyromonadaceaeandBacteroides.Cefoperazone created a susceptible community characterized by a drastic reduction in the community diversity, interactions, and a sustained increase in abundance of many facultative anaerobes. Lastly, clearance in streptomycin-treated mice was associated with the recovery of multiple members of thePorphyromonadaceae, with little overlap in the specificPorphyromonadaceaeobserved in the clindamycin treatment. Further elucidation of howC. difficilecolonization is cleared from different gut bacterial communities will improveC. difficileinfection treatments.

Importance

The community of microorganisms, known as the microbiota, in our intestines prevents pathogens, such asC. difficile, from establishing themselves and causing infection. This is known as colonization resistance. However, when a person takes antibiotics, their gut microbiota is disturbed. This disruption allowsC. difficileto colonize.C. difficileinfections (CDI) are primarily treated with antibiotics, which frequently leads to recurrent infections because the microbiota have not yet returned to a resistant state. The infection cycle often ends when the fecal microbiota from a presumed resistant person are transplanted into the susceptible person. Although this treatment is highly effective, we do not understand the mechanism of resistance. We hope to improve the treatment of CDI through elucidating how the bacterial community eliminatesC. difficilecolonization. We foundC. difficilewas able to colonize susceptible mice but was spontaneously eliminated in an antibiotic-treatment specific manner. These data indicate each community had different requirements for clearing colonization. Understanding how different communities clear colonization will reveal targets to improve CDI treatments.