title: Inflammatory bowel disease: exploring gut pathophysiology for novel therapeutic targets.
abstract: Ulcerative colitis and Crohn's disease are the 2 major phenotypes of inflammatory bowel disease (IBD), which are influenced by a complex interplay of immunological and genetic elements, though the precise etiology still remains unknown. With IBD developing into a globally prevailing disease, there is a need to explore new targets and a thorough understanding of the pathophysiological differences between the healthy and diseased gut could unearth new therapeutic opportunities. In this review, we provide an overview of the major aspects of IBD pathogenesis and thereafter present a comprehensive analysis of the gut pathophysiology leading to a discussion on some of the most promising targets and biologic therapies currently being explored. These include various gut proteins (CXCL-10, GATA-3, NKG2D, CD98, microRNAs), immune cells recruited to the gut (mast cells, eosinophils, toll-like receptors 2, 4), dysregulated proinflammatory cytokines (interleukin-6, -13, -18, -21), and commensal microbiota (probiotics and fecal microbiota transplantation). We also evaluate some of the emerging nonconventional therapies being explored in IBD treatment focusing on the latest developments in stem cell research, oral targeting of the gut-associated lymphoid tissue, novel anti-inflammatory signaling pathway targeting, adenosine deaminase inhibition, and the beneficial effects of antioxidant and nutraceutical therapies. In addition, we highlight the growth of biologics and their targets in IBD by providing information on the preclinical and clinical development of over 60 biopharmaceuticals representing the state of the art in ulcerative colitis and Crohn's disease drug development.
authors.affiliation: UCL School of Pharmacy, University College London, London, UK.
authors.forename: Vipul
authors.initials: V
authors.lastname: Yadav
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Felipe
authors.initials: F
authors.lastname: Varum
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bravo
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Esther
authors.initials: E
authors.lastname: Furrer
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bojic
authors.affiliation: UCL School of Pharmacy, University College London, London, UK. Electronic address: a.basit@ucl.ac.uk.
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Basit
mesh_terms: D000818:Animals; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D064307:Microbiota / Q000187:drug effects; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001688:Biological Products