Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction

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 communiti...

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Autores principales:	Jennifer M. Auchtung, Eva C. Preisner, James Collins, Armando I. Lerma, Robert A. Britton
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Clostridioides difficile FMT colonization resistance microbiome simplified communities Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5ce11a9930854f69b0a073e35eae139e
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spelling	oai:doaj.org-article:5ce11a9930854f69b0a073e35eae139e2021-11-15T15:30:51ZIdentification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction10.1128/mSphere.00387-202379-5042https://doaj.org/article/5ce11a9930854f69b0a073e35eae139e2020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00387-20https://doaj.org/toc/2379-5042ABSTRACT 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 operational 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. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and a significant health care burden. Fecal microbiota transplantation is highly effective at treating recurrent C. difficile disease; however, uncertainties about the undefined composition of fecal material and potential long-term unintended health consequences remain. These concerns have motivated studies to identify new communities of microbes with a simpler composition that will be effective at treating disease. This work describes a platform for rapidly identifying and screening new simplified communities for efficacy in treating C. difficile infection. Four new simplified communities of microbes with potential for development of new therapies to treat C. difficile disease are identified. While this platform was developed and validated to model infection with C. difficile, the underlying principles described in the paper could be easily modified to develop therapeutics to treat other gastrointestinal diseases.Jennifer M. AuchtungEva C. PreisnerJames CollinsArmando I. LermaRobert A. BrittonAmerican Society for MicrobiologyarticleClostridioides difficileFMTcolonization resistancemicrobiomesimplified communitiesMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridioides difficile FMT colonization resistance microbiome simplified communities Microbiology QR1-502
spellingShingle	Clostridioides difficile FMT colonization resistance microbiome simplified communities Microbiology QR1-502 Jennifer M. Auchtung Eva C. Preisner James Collins Armando I. Lerma Robert A. Britton Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction
description	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 operational 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. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and a significant health care burden. Fecal microbiota transplantation is highly effective at treating recurrent C. difficile disease; however, uncertainties about the undefined composition of fecal material and potential long-term unintended health consequences remain. These concerns have motivated studies to identify new communities of microbes with a simpler composition that will be effective at treating disease. This work describes a platform for rapidly identifying and screening new simplified communities for efficacy in treating C. difficile infection. Four new simplified communities of microbes with potential for development of new therapies to treat C. difficile disease are identified. While this platform was developed and validated to model infection with C. difficile, the underlying principles described in the paper could be easily modified to develop therapeutics to treat other gastrointestinal diseases.
format	article
author	Jennifer M. Auchtung Eva C. Preisner James Collins Armando I. Lerma Robert A. Britton
author_facet	Jennifer M. Auchtung Eva C. Preisner James Collins Armando I. Lerma Robert A. Britton
author_sort	Jennifer M. Auchtung
title	Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction
title_short	Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction
title_full	Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction
title_fullStr	Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction
title_full_unstemmed	Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction
title_sort	identification of simplified microbial communities that inhibit <named-content content-type="genus-species">clostridioides difficile</named-content> infection through dilution/extinction
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/5ce11a9930854f69b0a073e35eae139e
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Identification of Simplified Microbial Communities That Inhibit <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection through Dilution/Extinction

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