Modeling host-pathogen interactions in necrotizing enterocolitis

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.