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Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis

Arciero, JC and Ermentrout, GB and Upperman, JS and Vodovotz, Y and Rubin, JE (2010) Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis. PLoS ONE, 5 (4).

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Background: Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species). Methodology/Principal Findings: The objective of this study is to use a mathematical model to predict the conditions under which probiotics may be successful in promoting the health of infants suffering from NEC. An ordinary differential equation model is developed that tracks the populations of pathogenic and probiotic bacteria in the intestinal lumen and in the blood/tissue region. The permeability of the intestinal epithelial layer is treated as a variable, and the role of the inflammatory response is included. The model predicts that in the presence of probiotics health is restored in many cases that would have been otherwise pathogenic. The timing of probiotic administration is also shown to determine whether or not health is restored. Finally, the model predicts that probiotics may be harmful to the NEC patient under very specific conditions, perhaps explaining the detrimental effects of probiotics observed in some clinical studies. Conclusions/Significance: The reduced, experimentally motivated mathematical model that we have developed suggests how a certain general set of characteristics of probiotics can lead to beneficial or detrimental outcomes for infants suffering from NEC, depending on the influences of probiotics on defined features of the inflammatory response. © 2010 Arciero et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Arciero, JC
Ermentrout, GB
Upperman, JS
Vodovotz, Yvodovotz@pitt.eduVODOVOTZ
Rubin, JEjonrubin@pitt.eduJONRUBIN
ContributionContributors NameEmailPitt UsernameORCID
Date: 10 September 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0010066
Schools and Programs: Dietrich School of Arts and Sciences > Mathematics
Refereed: Yes
MeSH Headings: Enterocolitis, Necrotizing--pathology; Enterocolitis, Necrotizing--therapy; Humans; Infant, Newborn; Inflammation--microbiology; Inflammation--pathology; Intestinal Absorption; Models, Theoretical; Probiotics--adverse effects; Probiotics--therapeutic use; Treatment Outcome
Other ID: NLM PMC2856678
PubMed Central ID: PMC2856678
PubMed ID: 20419099
Date Deposited: 03 Aug 2012 20:55
Last Modified: 02 Feb 2019 15:56


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