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

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...

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Published inCommunications biology Vol. 7; no. 1; p. 135
Main Authors Douchant, Katya, He, Shu-Mei, Noordhof, Curtis, Greenlaw, Jill, Vancuren, Sarah, Schroeter, Kathleen, Allen-Vercoe, Emma, Sjaarda, Calvin, Vanner, Stephen J, Petrof, Elaine O, Sheth, Prameet M, Guzman, Mabel
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 27.01.2024
Nature Publishing Group UK
Nature Portfolio
Subjects
Animals
Anti-Bacterial Agents - pharmacology
Antibiotics
Bacteria
Clostridioides difficile
Clostridium Infections - microbiology
Clostridium Infections - prevention & control
Diarrhea
Diarrhea - microbiology
Diarrhea - prevention & control
Gastrointestinal tract
Gastrointestinal Tract - microbiology
Infections
Mice
Microbiomes
Microbiota
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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.
AbstractList 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.
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.An 18-member and a 4-member community consisting of commensal bacterial strains protected mice against C. difficile infection. The benefit of the 4-member community is mediated by secreted product(s) and not only by the bacteria, by proteolyzing clostridial toxins.
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.
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.
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. An 18-member and a 4-member community consisting of commensal bacterial strains protected mice against C. difficile infection. The benefit of the 4-member community is mediated by secreted product(s) and not only by the bacteria, by proteolyzing clostridial toxins.
ArticleNumber 135
Author Sheth, Prameet M
Guzman, Mabel
Sjaarda, Calvin
Noordhof, Curtis
Petrof, Elaine O
Vancuren, Sarah
Douchant, Katya
Vanner, Stephen J
He, Shu-Mei
Greenlaw, Jill
Schroeter, Kathleen
Allen-Vercoe, Emma
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Snippet Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to perturbations...
Abstract Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to...
Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to perturbations...
Abstract Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to...
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SubjectTerms Animals
Anti-Bacterial Agents - pharmacology
Antibiotics
Bacteria
Clostridioides difficile
Clostridium Infections - microbiology
Clostridium Infections - prevention & control
Diarrhea
Diarrhea - microbiology
Diarrhea - prevention & control
Gastrointestinal tract
Gastrointestinal Tract - microbiology
Infections
Mice
Microbiomes
Microbiota
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Title Defined microbial communities and their soluble products protect mice from Clostridioides difficile infection
URI https://www.ncbi.nlm.nih.gov/pubmed/38280981
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