Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae

Abstract

ABSTRACTThe indigenous microbial community of the gastrointestinal (GI) tract determines susceptibility toClostridium difficilecolonization and disease. Previous studies have demonstrated that antibiotic-treated mice challenged withC. difficileeither developed rapidly lethalC. difficileinfection or were stably colonized with mild disease. The GI microbial community of animals with mild disease was dominated by members of the bacterial familyLachnospiraceae, while the gut community in moribund animals had a predominance ofEscherichia coli. We investigated the roles of murineLachnospiraceaeandE. colistrains in colonization resistance againstC. difficilein germfree mice. MurineLachnospiraceaeandE. coliisolates were cultured from wild-type mice. The ability of each of these isolates to interfere withC. difficilecolonization was tested by precolonizing germfree mice with these bacteria 4 days prior to experimentalC. difficilechallenge. Mice precolonized with a murineLachnospiraceaeisolate, but not those colonized withE. coli, had significantly decreasedC. difficilecolonization, lower intestinal cytotoxin levels and exhibited less severe clinical signs and colonic histopathology. Infection of germfree mice or mice precolonized withE. coliwithC. difficilestrain VPI 10463 was uniformly fatal by 48 h, but only 20% mortality was seen at 2 days in mice precolonized with theLachnospiraceaeisolate prior to challenge with VPI 10463. These findings confirm that a single component of the GI microbiota, a murineLachnospiraceaeisolate, could partially restore colonization resistance againstC. difficile. Further study of the members within theLachnospiraceaefamily could lead to a better understanding of mechanisms of colonization resistance againstC. difficileand novel therapeutic approaches for the treatment and prevention ofC. difficileinfection.