a M2iSH, UMR 1071 Inserm, INRA USC-2018 , Institut Universitaire Technologique, Université Clermont Auvergne , Clermont-Ferrand 63001 , France.
b Univ. Lille, CNRS , UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle , 59000 Lille , France.
Expert Opin Ther Targets. 2017 Sep;21(9):837-847. doi: 10.1080/14728222.2017.1363184. Epub 2017 Aug 11.
Crohn's disease (CD) is a life-long chronic disorder characterized by intestinal inflammation. Current treatments for CD are directed towards abnormal immune responses rather than the intestinal bacteria that trigger intestinal inflammation. Areas covered: Adherent-Invasive Escherichia coli (AIEC) bacteria abnormally colonize the ileal mucosa in a subgroup of CD patients. They can promote or perpetuate chronic inflammation and are therefore an interesting therapeutic target. Various strategies that target these E. coli strains have been developed to promote their intestinal clearance. Here, we review current AIEC-targeted strategies, especially anti-adhesive strategies, that are based on the development of FimH antagonists. We discuss their potential as personalized microbiota-targeted treatments for CD patients abnormally colonized by AIEC. Expert opinion: A large panel of mannose-derived FimH antagonists were tested for their ability to inhibit E. coli adhesion to host cells. Documented reports suggest that monovalent mannosides are promising candidates that could represent a complementary therapeutic strategy to prevent intestinal inflammation in the E. coli-colonized CD patient subgroup. Ongoing research continues to improve the pharmacokinetic properties of mannosides, and hopefully, clinical trials will be performed in CD patients in the near future.
克罗恩病(CD)是一种终身慢性疾病,其特征是肠道炎症。目前针对 CD 的治疗方法针对的是异常的免疫反应,而不是引发肠道炎症的肠道细菌。
黏附侵袭性大肠杆菌(AIEC)细菌异常定植于 CD 患者亚组的回肠黏膜。它们可以促进或持续慢性炎症,因此是一个有趣的治疗靶点。已经开发了各种针对这些大肠杆菌菌株的策略来促进其肠道清除。在这里,我们综述了当前针对 AIEC 的策略,特别是基于 FimH 拮抗剂开发的抗黏附策略。我们讨论了它们作为针对 AIEC 异常定植的 CD 患者的个性化微生物组靶向治疗的潜力。
已经测试了大量的甘露糖衍生的 FimH 拮抗剂,以评估它们抑制大肠杆菌与宿主细胞黏附的能力。有文献报道称,单价甘露糖苷是很有前途的候选物,可能代表一种互补的治疗策略,可预防大肠杆菌定植的 CD 患者亚组的肠道炎症。目前正在进行研究以改善甘露糖苷的药代动力学特性,希望在不久的将来能在 CD 患者中进行临床试验。