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

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

Author information

1
a M2iSH, UMR 1071 Inserm, INRA USC-2018 , Institut Universitaire Technologique, Université Clermont Auvergne , Clermont-Ferrand 63001 , France.
2
b Univ. Lille, CNRS , UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle , 59000 Lille , France.
3
c Université de Lyon, Lyon, France ; INSA-Lyon, Ingénierie des Matériaux Polymères (IMP), Villeurbanne, France ; CNRS, UMR 5223, Ingénierie des Matériaux Polymères , Villeurbanne , France.
4
d INSA-Lyon , IMP , Villeurbanne , France.
5
e UMR 5223, Ingénierie des Matériaux Polymères , CNRS , Villeurbanne , France.
6
f CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques , LUNAM Université , Nantes Cedex 3 , France.

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

PMID:
28762293
DOI:
10.1080/14728222.2017.1363184
[Indexed for MEDLINE]

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