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The IBD interactome: an integrated view of aetiology, pathogenesis and therapy

Nature Reviews Gastroenterology & Hepatology volume 14, pages 739–749 (2017)Cite this article

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Abstract

Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '–ome') in isolation without consideration of the interaction among all relevant –omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual –omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple –omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.

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Figure 1: Role of epigenetic modifications in the development of IBD.
Figure 2: Knowledge expansion and building of the IBD interactome.
Figure 3: Building and therapeutic targeting of the IBD interactome.

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Authors and Affiliations

  1. Department of Gastroenterology & Multidisciplinary Research Laboratory, Federal University of Rio de Janeiro, 21941–913, Rio de Janeiro, Brazil

    Heitor S. P. de Souza

  2. Department of Pathobiology, Department of Gastroenterology and Hepatology, Lerner Research Institute, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, 44195, Ohio, USA

    Claudio Fiocchi

  3. Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, Center for Systems Biomedicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, 90095, California, USA

    Dimitrios Iliopoulos

Authors
  1. Heitor S. P. de Souza
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  2. Claudio Fiocchi
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  3. Dimitrios Iliopoulos
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All authors contributed equally to all aspects of this manuscript.

Corresponding author

Correspondence to Claudio Fiocchi.

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The authors declare no competing financial interests.

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Supplementary information S1 (figure)

Screenshot of CellFateScout result. (PDF 613 kb)

Supplementary information S2 (figure)

Flow diagram for utilization of human IBD clinical biosamples for integrated –omics analyses. (PDF 439 kb)

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de Souza, H., Fiocchi, C. & Iliopoulos, D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 14, 739–749 (2017). https://doi.org/10.1038/nrgastro.2017.110

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