Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection

Abstract Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to perturbations of the bacterial community in the gastrointestinal tract, called the gastrointestinal microbiota. Repairing the gastrointestinal micr...

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Main Authors: Katya Douchant, Shu-Mei He, Curtis Noordhof, Jill Greenlaw, Sarah Vancuren, Kathleen Schroeter, Emma Allen-Vercoe, Calvin Sjaarda, Stephen J. Vanner, Elaine O. Petrof, Prameet M. Sheth, Mabel Guzman
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-05778-6
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author Katya Douchant
Shu-Mei He
Curtis Noordhof
Jill Greenlaw
Sarah Vancuren
Kathleen Schroeter
Emma Allen-Vercoe
Calvin Sjaarda
Stephen J. Vanner
Elaine O. Petrof
Prameet M. Sheth
Mabel Guzman
author_facet Katya Douchant
Shu-Mei He
Curtis Noordhof
Jill Greenlaw
Sarah Vancuren
Kathleen Schroeter
Emma Allen-Vercoe
Calvin Sjaarda
Stephen J. Vanner
Elaine O. Petrof
Prameet M. Sheth
Mabel Guzman
author_sort Katya Douchant
collection DOAJ
description Abstract Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to perturbations of the bacterial community in the gastrointestinal tract, called the gastrointestinal microbiota. Repairing the gastrointestinal microbiota by introducing lab-designed bacterial communities, or defined microbial communities, has recently shown promise as therapeutics against C.difficile infection, however, the mechanisms of action of defined microbial communities remain unclear. Using an antibiotic- C.difficile mouse model, we report the ability of an 18-member community and a refined 4-member community to protect mice from two ribotypes of C.difficile (CD027, CD078; p < 0.05). Furthermore, bacteria-free supernatant delivered orally to mice from the 4-member community proteolyzed C.difficile toxins in vitro and protected mice from C.difficile infection in vivo (p < 0.05). This study demonstrates that bacteria-free supernatant is sufficient to protect mice from C.difficile; and could be further explored as a therapeutic strategy against C.difficile infection.
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spelling doaj.art-7a4b2c5a7efa4d30a08a1140befa2ea52024-03-05T16:38:43ZengNature PortfolioCommunications Biology2399-36422024-01-017111210.1038/s42003-024-05778-6Defined microbial communities and their soluble products protect mice from Clostridioides difficile infectionKatya Douchant0Shu-Mei He1Curtis Noordhof2Jill Greenlaw3Sarah Vancuren4Kathleen Schroeter5Emma Allen-Vercoe6Calvin Sjaarda7Stephen J. Vanner8Elaine O. Petrof9Prameet M. Sheth10Mabel Guzman11The Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterThe Gastrointestinal Disease Research Unit (GIDRU), Kingston Health Sciences CenterAbstract Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to perturbations of the bacterial community in the gastrointestinal tract, called the gastrointestinal microbiota. Repairing the gastrointestinal microbiota by introducing lab-designed bacterial communities, or defined microbial communities, has recently shown promise as therapeutics against C.difficile infection, however, the mechanisms of action of defined microbial communities remain unclear. Using an antibiotic- C.difficile mouse model, we report the ability of an 18-member community and a refined 4-member community to protect mice from two ribotypes of C.difficile (CD027, CD078; p < 0.05). Furthermore, bacteria-free supernatant delivered orally to mice from the 4-member community proteolyzed C.difficile toxins in vitro and protected mice from C.difficile infection in vivo (p < 0.05). This study demonstrates that bacteria-free supernatant is sufficient to protect mice from C.difficile; and could be further explored as a therapeutic strategy against C.difficile infection.https://doi.org/10.1038/s42003-024-05778-6
spellingShingle Katya Douchant
Shu-Mei He
Curtis Noordhof
Jill Greenlaw
Sarah Vancuren
Kathleen Schroeter
Emma Allen-Vercoe
Calvin Sjaarda
Stephen J. Vanner
Elaine O. Petrof
Prameet M. Sheth
Mabel Guzman
Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
Communications Biology
title Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
title_full Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
title_fullStr Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
title_full_unstemmed Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
title_short Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
title_sort defined microbial communities and their soluble products protect mice from clostridioides difficile infection
url https://doi.org/10.1038/s42003-024-05778-6
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