Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis.
Using a mathematical model to analyze the role of probiotics and inflammation in necrotizing enterocolitis.
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DOI：
10.1371/journal.pone.0010066
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发表时间：
2010-04-19
期刊：
影响因子：
3.7
通讯作者：
Rubin JE
中科院分区：
文献类型：
--
作者：
Arciero JC;Ermentrout GB;Upperman JS;Vodovotz Y;Rubin JE
坏死性小肠结肠炎（NEC）是早产儿胃肠道的严重疾病，被认为与肠道生理不成熟和肠道正常植物群水平改变有关。了解导致NEC病理的因素可能会导致治疗策略的发展，旨在重建上皮细胞壁的完整性，并防止NEC炎症的传播。几项研究表明，使用益生菌（有益菌）治疗的新生儿NEC的发病率和严重程度降低。本研究的目的是使用数学模型来预测益生菌可能成功促进NEC婴儿健康的条件。开发了一种常微分方程模型，该模型跟踪肠腔和血液/组织区域中的致病菌和益生菌的种群。肠上皮层的渗透性被视为一个变量，包括炎症反应的作用。该模型预测，在益生菌的存在下，在许多情况下，原本是致病的健康得到了恢复。益生菌给药的时机也被证明可以确定健康是否恢复。最后，该模型预测，在非常特定的条件下，益生菌可能对NEC患者有害，这可能解释了在一些临床研究中观察到的益生菌的有害作用。我们已经开发的简化的、实验驱动的数学模型表明，益生菌的某些一般特征集如何导致患有NEC的婴儿的有益或有害结果，这取决于益生菌对炎症反应的定义特征的影响。
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). 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. 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.