Identification of Simplified Microbial Communities That Inhibit Clostridioides difficile Infection through Dilution/Extinction

Authors

Jennifer M. Auchtung, Baylor College of Medicine, Houston & University of Nebraska—LincolnFollow
Eva C. Preisner, Baylor College of Medicine, Houston
James Collins, Baylor College of Medicine, Houston & University of Louisville School of Medicine
Armando I. Lerma, Baylor College of Medicine, Houston & University of Louisville School of Medicine
Robert A. Britton, Baylor College of Medicine, Houston

ORCID IDs

https://orcid.org/0000-0003-3038-583X

https://orcid.org/0000-0001-8983-9539

Date of this Version

2020

Citation

Auchtung JM, Preisner EC, Collins J, Lerma AI, Britton RA. 2020. Identification of simplified microbial communities that inhibit Clostridioides difficile infection through dilution/ extinction. mSphere 5:e00387-20. https://doi .org/10.1128/mSphere.00387-20.

Comments

2020 Auchtung et al.

Abstract

The gastrointestinal microbiome plays an important role in limiting susceptibility to infection with Clostridioides difficile. To better understand the ecology of bacteria important for C. difficile colonization resistance, we developed an experimental platform to simplify complex communities of fecal bacteria through dilution and rapidly screen for their ability to resist C. difficile colonization after challenge, as measured by 􏰀100-fold reduction in levels of C. difficile in challenged communities. We screened 76 simplified communities diluted from cultures of six fecal donors and identified 24 simplified communities that inhibited C. difficile colonization in vitro. Sequencing revealed that simplified communities were composed of 19 to 67 opera- tional taxonomic units (OTUs) and could be partitioned into four distinct community types. One simplified community could be further simplified from 56 to 28 OTUs through dilution and retain the ability to inhibit C. difficile. We tested the efficacy of seven simplified communities in a humanized microbiota mouse model. We found that four communities were able to significantly reduce the severity of the initial C. difficile infection and limit susceptibility to disease relapse. Analysis of fecal microbiomes from treated mice demonstrated that simplified communities accelerated recovery of indigenous bacteria and led to stable engraftment of 19 to 22 OTUs from simplified communities. Overall, the insights gained through the identification and characterization of these simplified communities increase our understanding of the microbial dynamics of C. difficile infection and recovery.