The potential of FimH as a novel therapeutic target for the treatment of Crohn's disease

Expert Opin Ther Targets. 2017 Sep;21(9):837-847. doi: 10.1080/14728222.2017.1363184. Epub 2017 Aug 11.

Abstract

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.

Keywords: Escherichia coli; FimH antagonists; mannosides; microbiota-targeting therapy; personalized therapy.

Publication types

  • Review

MeSH terms

  • Adhesins, Escherichia coli
  • Animals
  • Crohn Disease / drug therapy*
  • Crohn Disease / microbiology
  • Crohn Disease / pathology
  • Drug Design
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / physiopathology
  • Fimbriae Proteins / antagonists & inhibitors*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / microbiology
  • Inflammation / pathology
  • Mannosides / administration & dosage
  • Mannosides / pharmacokinetics
  • Molecular Targeted Therapy

Substances

  • Adhesins, Escherichia coli
  • Mannosides
  • fimH protein, E coli
  • Fimbriae Proteins