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Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae
Open accessAbstract
The indigenous microbial community of the gastrointestinal (GI) tract determines susceptibility to Clostridium difficile colonization and disease. Previous studies have demonstrated that antibiotic-treated mice challenged with C. difficile either developed rapidly lethal C. difficile infection or were stably colonized with mild disease. The GI microbial community of animals with mild disease was dominated by members of the bacterial family Lachnospiraceae, while the gut community in moribund animals had a predominance of Escherichia coli. We investigated the roles of murine Lachnospiraceae and E. coli strains in colonization resistance against C. difficile in germfree mice. Murine Lachnospiraceae and E. coli isolates were cultured from wild-type mice. The ability of each of these isolates to interfere with C. difficile colonization was tested by precolonizing germfree mice with these bacteria 4 days prior to experimental C. difficile challenge. Mice precolonized with a murine Lachnospiraceae isolate, but not those colonized with E. coli, had significantly decreased C. difficile colonization, lower intestinal cytotoxin levels and exhibited less severe clinical signs and colonic histopathology. Infection of germfree mice or mice precolonized with E. coli with C. difficile strain VPI 10463 was uniformly fatal by 48 h, but only 20% mortality was seen at 2 days in mice precolonized with the Lachnospiraceae isolate prior to challenge with VPI 10463. These findings confirm that a single component of the GI microbiota, a murine Lachnospiraceae isolate, could partially restore colonization resistance against C. difficile. Further study of the members within the Lachnospiraceae family could lead to a better understanding of mechanisms of colonization resistance against C. difficile and novel therapeutic approaches for the treatment and prevention of C. difficile infection.
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“Furthermore successful FMT restores members of Lachnospiraceae and other butyrate producing organisms supporting their potential role in outcompeting C. difficile.50”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [50]
In the citing paper
“Additionally, changes in microbial community structure such as restoration of key Firmicutes and Bacteroidetes species with a decrease in Proteobacteria appear to be required in order to outcompete C. difficile.50”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [50]
In the citing paper
“An important factor determining success of fecal transplant is restoration of microbial diversity following treatment50.”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [50]
In the citing paper
“Bacterial strains [54, 118, 119] and metabolites [54] associated with protection from C. difficile have now been identified”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [119]
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Metadata
- Authors
- Reeves, A. E., Koenigsknecht, M. J., Bergin, I. L., & Young, V. B.
- Affiliations
- University of Michigan (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2012-11
- Volume
- 80
- Issue
- 11
- Pages
- 3786-3794
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC3486043
- OpenAlex
- W2122459017
- Cited by
- 292
- References
- 47
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 14 · 2023: 13 · 2022: 25 · 2021: 32 · 2020: 25 · 2019: 23 · 2018: 28 · 2017: 21 · 2016: 23 · 2015: 26 · 2014: 23 · 2013: 18
- FWCI
- 14.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (U19AI090871, AI090871)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK089503, R01DK070875, P30DK089503)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Clostridium difficile, colonization resistance, Lachnospiraceae, gut microbiota, germ-free mice, Escherichia coli, Clostridium difficile infection, colonic histopathology, antibiotic-treated mice
- MeSH terms
- Animals, Escherichia coli, Germ-Free Life, Mice, Inbred C57BL, Phylogeny, RNA, Ribosomal, 16S, Colony Count, Microbial, Clostridioides difficile, Gram-Positive Endospore-Forming Rods, Gastrointestinal Tract, Mice, Metagenome
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