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Intestinal bacteria antagonistic to Clostridium difficile in mice
Abstract:
Overgrowth by Clostridium difficile has been reported in conventional mice injected intraperitoneally with ampicillin. In this study, we aimed to determine which types of indigenous intestinal bacteria were eliminated by ampicillin to allow overgrowth by C. difficile. C. difficile overgrowth was associated with a decrease in the numbers of lactobacilli, an increase in bacteroidaceae and a slight decrease in the frequency of isolation of fusiform-shaped bacteria (clostridia). C. difficile cytotoxin was detected in caeca from mice in which the numbers of C. difficile were greater than 10(5) per gram of faeces. Gnotobiotic mice were inoculated with various groups of intestinal anaerobes to determine which members of the indigenous flora would antagonize C. difficile. Gnotobiotic mice inoculated with three strains of lactobacilli, 37 strains of bacteroides or 46 strains of clostridia isolated from limited-flora mice were unable to eliminate C. difficile. C. difficile was eliminated, however, from the gastrointestinal tracts of gnotobiotic mice inoculated with whole faeces or chloroform-treated faeces from conventional mice or whole faeces from limited-flora mice containing only clostridia.
Insights
Ampicillin treatment reduced beneficial gut bacteria, allowing Clostridium difficile overgrowth. Restoration of diverse gut microbiota, including specific clostridia, prevented C. difficile proliferation in mice.
Area of Science:
- Microbiology
- Gastroenterology
- Animal Models
Background:
- Clostridium difficile overgrowth is a known issue in mice treated with ampicillin.
- Understanding the specific indigenous bacteria affected by ampicillin is crucial for preventing C. difficile proliferation.
Purpose of the Study:
- To identify intestinal bacteria eliminated by ampicillin that permit C. difficile overgrowth.
- To determine which indigenous gut bacteria antagonize C. difficile growth.
Main Methods:
- Conventional mice were injected with ampicillin, and their gut microbiota composition was analyzed.
- Gnotobiotic mice were inoculated with specific bacterial groups or fecal samples to assess C. difficile colonization resistance.
Main Results:
- Ampicillin treatment led to decreased lactobacilli and increased bacteroidaceae, correlating with C. difficile overgrowth.
- Lactobacilli, bacteroides, and some clostridia strains did not prevent C. difficile colonization.
- Colonization resistance was established by inoculating with whole feces from conventional or limited-flora mice, indicating the importance of a diverse microbiota.
Conclusions:
- The elimination of specific indigenous gut bacteria by ampicillin facilitates Clostridium difficile overgrowth.
- A diverse intestinal microbiota, particularly certain clostridia, is essential for preventing C. difficile colonization.