Pre-colonization with the commensal fungus Candida albicans reduces murine susceptibility to Clostridium difficile infection
Pre-colonization with the commensal fungus Candida albicans reduces murine susceptibility to Clostridium difficile infection
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DOI：
10.1080/19490976.2018.1465158
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发表时间：
2018-01-01
期刊：
影响因子：
12.2
通讯作者：
Kumamoto, Carol A.
中科院分区：
文献类型：
--
作者：
Markey, Laura;Shaban, Lamyaa;Kumamoto, Carol A.
艰难梭菌（Clostridium difficile）是一种主要的医院病原体，在美国每年造成近50万例感染和2.7万例死亡。此前的抗生素治疗是艰难梭菌感染（CDI）的主要危险因素，这使得人们认识到共生微生物在对CDI的耐药性中起着关键作用。由于复发率高，目前对CDI的抗生素治疗仅部分成功。因此，人们有兴趣了解微生物对CDI敏感性的影响，以支持益生菌微生物或整个微生物群落（例如，粪便微生物群移植）患者的治疗。本文报道的结果表明，在小鼠模型中，人类共生真菌白色念珠菌的定植可以防止致命的CDI。白色念珠菌的定植不增加宿主的定植抗性。相反，我们的研究结果表明，白色念珠菌定植的一个作用是增强保护性免疫反应。与未定殖白色念珠菌的小鼠相比，预先定殖白色念珠菌的小鼠在艰难梭菌攻击后感染组织中表达了更高水平的IL-17A。细胞因子IL-17A被证明对没有白色念珠菌定植的小鼠的致命小鼠CDI具有保护作用。白色念珠菌的定植与肠道微生物群中某些细菌成分的丰度变化有关。因此，白色念珠菌的定植改变了肠道生态系统，提高了艰难梭菌攻击后的存活率。这些发现证明了白色念珠菌肠道定植的一个新的有益作用。
Clostridium difficile is a major nosocomial pathogen responsible for close to half a million infections and 27,000 deaths annually in the U.S. Preceding antibiotic treatment is a major risk factor for C. difficile infection (CDI) leading to recognition that commensal microbes play a key role in resistance to CDI. Current antibiotic treatment of CDI is only partially successful due to a high rate of relapse. As a result, there is interest in understanding the effects of microbes on CDI susceptibility to support treatment of patients with probiotic microbes or entire microbial communities (e.g., fecal microbiota transplantation). The results reported here demonstrate that colonization with the human commensal fungus Candida albicans protects against lethal CDI in a murine model. Colonization with C. albicans did not increase the colonization resistance of the host. Rather, our findings showed that one effect of C. albicans colonization was to enhance a protective immune response. Mice pre-colonized with C. albicans expressed higher levels of IL-17A in infected tissue following C. difficile challenge compared to mice that were not colonized with C. albicans. Administration of cytokine IL-17A was demonstrated to be protective against lethal murine CDI in mice not colonized with C. albicans. C. albicans colonization was associated with changes in the abundance of some bacterial components of the gut microbiota. Therefore, C albicans colonization altered the gut ecosystem, enhancing survival after C. difficile challenge. These findings demonstrate a new, beneficial role for C. albicans gut colonization.