Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0435, USA.
Curr Opin Infect Dis. 2013 Oct;26(5):447-53. doi: 10.1097/01.qco.0000433318.82618.c6.
Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in the healthcare setting. An emerging consensus suggests that CDI is caused by pathogenic toxin production, gut microbial dysbiosis and altered host inflammatory responses. The aim of this review is to summarize and highlight recent advances focused on CDI pathogenic mechanisms.
Potential paradigm shifts relating to the mechanisms of toxin action and inhibition have recently been reported, with new insights into spore germination and surface protein function also gaining traction. Multiomic analysis of microbiome dysbiosis has identified important CDI-associated microbial community shifts that may form the basis of future targeted bacteriotherapy, and functional metabolite biomarkers that require further characterization. Classical innate and adaptive immunity against CDI is rapidly being delineated, with novel innate S-nitrosylation signals also being identified.
Studies in patients and animal disease models are shedding new light on the critical roles of the microbiota, metabolome and host responses in primary and recurrent CDI. An improved understanding of the CDI disease pathogenesis will provide the basis for developing new therapies for treating disease and preventing recurrence.
艰难梭菌感染（CDI）是医疗环境中抗生素相关性腹泻和伪膜性结肠炎的主要原因。新出现的共识认为，CDI 是由致病毒素的产生、肠道微生物失调和宿主炎症反应改变引起的。本综述的目的是总结和强调 CDI 发病机制的最新进展。
最近有报道称，与毒素作用和抑制相关的潜在范式转变，对孢子萌发和表面蛋白功能的新见解也受到关注。微生物组失调的多组学分析已经确定了与 CDI 相关的重要微生物群落变化，这可能为未来的靶向细菌治疗奠定基础，并确定了需要进一步表征的功能性代谢物生物标志物。针对 CDI 的经典先天和适应性免疫正在迅速被描绘出来，新的先天 S-亚硝基化信号也被确定。
对患者和动物疾病模型的研究揭示了微生物群、代谢组和宿主反应在初次和复发性 CDI 中的关键作用。对 CDI 发病机制的深入了解将为治疗疾病和预防复发提供新疗法的基础。
