Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae
Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae
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DOI：
10.1128/iai.00647-12
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发表时间：
2012-11-01
影响因子：
3.1
通讯作者：
Young, Vincent B.
中科院分区：
文献类型：
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作者：
Reeves, Angela E.;Koenigsknecht, Mark J.;Young, Vincent B.
胃肠道（GI）的本地微生物群落决定了艰难梭菌定植和疾病的易感性。先前的研究表明，用艰难梭菌攻击抗生素治疗的小鼠要么迅速发展为致命的艰难梭菌感染，要么稳定地定植为轻度疾病。轻症动物胃肠道微生物群落以毛缕菌科细菌家族成员为主，而濒死动物肠道菌群以大肠杆菌为主。我们研究了鼠毛螺杆菌科和大肠杆菌菌株在无菌小鼠体内对艰难梭菌的定殖抗性中的作用。从野生型小鼠中培养鼠毛螺杆菌科和大肠杆菌分离株。这些分离株干扰艰难梭菌定植的能力是在实验艰难梭菌攻击前4天用这些细菌预定植无菌小鼠来测试的。用鼠毛螺杆菌分离物预先定殖的小鼠，而不是用大肠杆菌定殖的小鼠，其艰难梭菌定殖显著减少，肠道细胞毒素水平较低，临床症状和结肠组织病理学较轻。无菌小鼠或携带艰难梭菌菌株VPI 10463的大肠杆菌预定植的小鼠在48小时内均致死性，但在用VPI 10463攻毒前，用毛螺科菌株预定植的小鼠在2天内死亡率仅为20%。这些发现证实，胃肠道微生物群的单一成分，小鼠毛缕菌科分离物，可以部分恢复对艰难梭菌的定植抗性。进一步研究毛螺旋菌科成员，可以更好地了解艰难梭菌的定植抗性机制，并为治疗和预防艰难梭菌感染提供新的治疗方法。
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.