A. Gemelli Hospital, Division of Internal Medicine and Gastroenterology, Department of Internal Medicine, School of Medicine and Surgery, Catholic University, 8, 00168 Rome, Italy.
J Immunol Res. 2014;2014:462740. doi: 10.1155/2014/462740. Epub 2014 Jun 5.
Recurrent Clostridium difficile infection represents a burdensome clinical issue whose epidemiology is increasing worldwide. The pathogenesis is not yet completely known. Recent observations suggest that the alteration of the intestinal microbiota and impaired innate immunity may play a leading role in the development of recurrent infection. Various factors can cause dysbiosis. The causes most involved in the process are antibiotics, NSAIDs, acid suppressing therapies, and age. Gut microbiota impairment can favor Clostridium difficile infection through several mechanisms, such as the alteration of fermentative metabolism (especially SCFAs), the alteration of bile acid metabolism, and the imbalance of antimicrobial substances production. These factors alter the intestinal homeostasis promoting the development of an ecological niche for Clostridium difficile and of the modulation of immune response. Moreover, the intestinal dysbiosis can promote a proinflammatory environment, whereas Clostridium difficile itself modulates the innate immunity through both toxin-dependent and toxin-independent mechanisms. In this narrative review, we discuss how the intestinal microbiota modifications and the modulation of innate immune response can lead to and exacerbate Clostridium difficile infection.
复发性艰难梭菌感染是一个棘手的临床问题，其在全球范围内的流行病学正在不断增加。其发病机制尚不完全清楚。最近的观察结果表明，肠道微生物群的改变和先天免疫受损可能在复发性感染的发展中起主要作用。各种因素可导致肠道菌群失调。在这个过程中，最相关的原因是抗生素、非甾体抗炎药、胃酸抑制疗法和年龄。肠道微生物群的损伤可通过多种机制促进艰难梭菌感染，例如发酵代谢（尤其是短链脂肪酸）的改变、胆汁酸代谢的改变以及抗菌物质产生的失衡。这些因素改变了肠道内环境，促进了艰难梭菌的生态位形成和免疫反应的调节。此外，肠道菌群失调可促进炎症环境，而艰难梭菌本身通过毒素依赖和非依赖机制调节先天免疫。在这篇叙述性综述中，我们讨论了肠道微生物群的改变和先天免疫反应的调节如何导致并加剧艰难梭菌感染。
