Crohn's disease and ulcerative colitis, collectively termed inflammatory bowel disease
(IBD), are immunologic disorders that represent the prototypes of chronic intestinal
inflammation. Their pathogenesis involves the dysregulated interaction between the
intestinal microbiota and the gut-associated mucosal immune system that takes place
when genetically predisposed individuals are exposed to detrimental environmental
triggers. In recent years, the therapeutic dogma in IBD has shifted away from the
administration of nonspecific immunosuppressives toward a pathway-based approach.
In this review, we present an outlook of IBD treatment based on this new conceptual
approach. Firstly, we will provide an overview of the major aspects of IBD pathogenesis
with emphasis on specific pathway-based defects. Secondly, we will examine in detail
the development of novel therapeutic approaches that can be used to target genetics,
dysbiosis, the epithelial barrier, proinflammatory cytokines, and leukocyte trafficking.
Most of these strategies are still in the developmental phase, but promising approaches
include fecal microbiota transplantation as a means to correct IBD-related dysbiosis;
administration of modified phosphatidylcholine to enhance the function of the intestinal
mucous and tighten the defective epithelial barrier; the reduction of over-reactive
proinflammatory pathways through the blockade of novel, nontumor necrosis factor inflammatory
mediators via monoclonal antibodies against the common p40 chain of interleukin (IL-12)
and IL-23, Janus kinase inhibitors, or antisense oligonucleotides against inhibitors
of the immunosuppressive cytokine transforming growth factor-β1; and finally, inhibition
of leukocyte trafficking to the gut via neutralization of the gut-specific α4β7 integrin. Availability of such diverse treatment modalities with specific pathway-based
targets will increase the therapeutic options for patients with IBD.
Abbreviations:
CAI (Colitis Activity Index), CCL25 (Chemokine C Ligand 25), CD (Crohn's Disease), FMT (Fecal Microbiota Transplantation), GI (Gastroeintestinal), HSCT (Hematopoietic Stem Cell Transplantation), IBD (Inflammatory Bowel Disease), IL (Interleukin), JAK (Janus Kinase), JK (Janus Kinase), MAdCAM-1 (Mucosal Addressin Cell Adhesion Molecule-1), PC (Phosphatidylcholine), PML (Progressive Multifocal Leukoencephalopahty), SCCAI (Simple Clinical Colitis Activity Index), SMAD (Similar to Mothers against Decapentaplegic), TECK (Thymus-Expressed Chemokine), TGF (Transforming Growth Factor), Th (T helper), TNF (Tumor Necrosis Factor), UC (Ulcerative Colitis)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: September 07, 2015
Accepted:
September 2,
2015
Received in revised form:
September 1,
2015
Received:
June 11,
2015
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
