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Modeling Host–Pathogen Interactions in Necrotizing Enterocolitis

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Complex Systems and Computational Biology Approaches to Acute Inflammation

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Abstract

Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract that affects primarily premature infants and is characterized by physiological immaturity of the intestine, abnormal bacterial colonization of the gut, and disordered inflammatory signaling. The severity of NEC coupled to a lack of effective therapy has motivated the use of systems approaches including computational modeling to gain a fuller insight into both mechanism and therapy for NEC. Here, we explore ordinary differential equation, partial differential equation, and agent based mathematical models that incorporate clinical and experimental observations to study key interactions of bacteria, the intestinal epithelial barrier, and the inflammatory response in NEC. The three different modeling approaches provide techniques to obtain time-dependent and/or space-dependent information about the complex interplay between host defense mechanisms and bacterial virulence. The strengths, shortcomings, and applicability of each model type are examined. Ultimately, theoretical models can help to unravel the complex network of factors that contribute to the pathology of NEC and guide the development of treatment strategies aimed at reestablishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC.

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Authors and Affiliations

  1. Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, 402 N. Blackford St., LD 270D, Indianapolis, IN, 46202, USA

    Julia Arciero Ph.D.

  2. Department of Mathematical Sciences, University of Pittsburgh, 301 Thackeray Hall, Pittsburgh, PA, 15217, USA

    Jared Barber Ph.D.

  3. Department of General Surgery, University of Chicago Hospitals, 5841 S. Maryland (MC 5094), Chicago, IL, 60637, USA

    Moses Kim M.D.

Authors
  1. Julia Arciero Ph.D.
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  2. Jared Barber Ph.D.
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  3. Moses Kim M.D.
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Correspondence to Julia Arciero Ph.D. .

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Editors and Affiliations

  1. University of Pittsburgh Inflammation and Regenerative Modeling, Pittsburgh, Pennsylvania, USA

    Yoram Vodovotz

  2. University of Chicago Medical Center MC 5094, Chicago, Illinois, USA

    Gary An

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Arciero, J., Barber, J., Kim, M. (2013). Modeling Host–Pathogen Interactions in Necrotizing Enterocolitis. In: Vodovotz, Y., An, G. (eds) Complex Systems and Computational Biology Approaches to Acute Inflammation. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8008-2_13

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