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  • Review Article
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Towards a systems view of IBS

Nature Reviews Gastroenterology & Hepatology volume 12, pages 592–605 (2015)Cite this article

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Key Points

  • Physiological and molecular alterations have been identified in the brain–gut axis of human and rodent models of IBS, yet a comprehensive disease model to guide effective drug development has not emerged

  • Studies have identified distinct brain signatures in patients with IBS, which provide plausible neurobiological substrates of many previously reported behavioural and psychosocial observations

  • Emerging evidence demonstrates correlations of these brain signatures with alterations in genetics, immune system and gut microbiota in IBS, even though the causality of these interactions remains unknown

  • A systems-biology-based model is proposed to integrate the growing number of central, peripheral and behavioural IBS-related alterations, and to identify targets for more effective therapies

Abstract

Despite an extensive body of reported information about peripheral and central mechanisms involved in the pathophysiology of IBS symptoms, no comprehensive disease model has emerged that would guide the development of novel, effective therapies. In this Review, we will first describe novel insights into some key components of brain–gut interactions, starting with the emerging findings of distinct functional and structural brain signatures of IBS. We will then point out emerging correlations between these brain networks and genomic, gastrointestinal, immune and gut-microbiome-related parameters. We will incorporate this new information, as well as the reported extensive literature on various peripheral mechanisms, into a systems-based disease model of IBS, and discuss the implications of such a model for improved understanding of the disorder, and for the development of more-effective treatment approaches in the future.

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Figure 1: Brain–gut axis.
Figure 2: Brain networks contributing to IBS symptoms.
Figure 3: Cross-sectional integrated brain–gut model of IBS pathophysiology.
Figure 4: Longitudinal brain–gut model of IBS pathophysiology.
Figure 5: Systems biological model of IBS.

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Acknowledgements

Supported by funding National Institutes of Health grants P50 DK064539 (E.A.M.), R01 DK048351 (E.A.M.) and P30 DK041301 (E.R.). The authors thank Cathy Liu and Arpana Gupta for invaluable editorial assistance.

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Authors and Affiliations

  1. Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, 90095-7378, CA, USA

    Emeran A. Mayer, Jennifer S. Labus & Steven W. Cole

  2. Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, 90095-7378, CA, USA

    Kirsten Tillisch

  3. West Los Angeles VA Medical Center, 11301 Wilshire Boulevard, Los Angeles, 90073, CA, USA

    Kirsten Tillisch

  4. Institute for Genomics and Bioinformatics, University of California at Irvine, 4038 Bren Hall, Irvine, 92697-3435, CA, USA

    Pierre Baldi

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Contributions

The article was conceptualized and composed by E.A.M. Inputs to the following sections came from the following co-authors: immune system (S.W.C.); brain networks (J.S.L.); gut microbiota (K.T.); and systems biology (P.B.).

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Correspondence to Emeran A. Mayer.

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Mayer, E., Labus, J., Tillisch, K. et al. Towards a systems view of IBS. Nat Rev Gastroenterol Hepatol 12, 592–605 (2015). https://doi.org/10.1038/nrgastro.2015.121

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