DeBoer Mark D, Vijayakumar Vidhya, Gong Meiqing, Fowlkes John L, Smith Rachel M, Ruiz-Perez Fernando, Nataro James P
Division of Pediatric Endocrinology, University of Virginia, Charlottesville, VA; Department of Pediatrics, University of Virginia, Charlottesville, VA.
Department of Pediatrics, University of Virginia, Charlottesville, VA; Division of Pediatric Infectious Disease, University of Virginia, Charlottesville, VA.
Nutr Res. 2017 Mar;39:34-42. doi: 10.1016/j.nutres.2017.02.005. Epub 2017 Feb 7.
In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C rodentium-infected, partially-attenuated C rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the wild-type C rodentium group). Relative to the uninfected group, mice infected with wild-type C rodentium exhibited temporal associations of lower food intake, weight loss, linear-growth failure, higher IL-6 and TNF-α and lower IGF-1. However, relative to the pair-fed group, the C rodentium-infected group only differed significantly by linear growth and systemic inflammatory cytokines. Between post-infection days 15-20, the infected group exhibited resolution of systemic inflammation. Between days 16-20, both wild-type C rodentium and pair-fed groups exhibited rapid linear-growth velocities exceeding the uninfected and mutant C rodentium groups; during this time levels of IGF-1 increased to match the uninfected group. We submit this as a model providing important opportunities to study mechanisms of catch-up growth related to intestinal inflammation. We conclude that in addition to known effects of weight loss, infection with C rodentium induces linear-growth failure potentially related to systemic inflammation and low levels of IGF-1, with catch-up of linear growth following resolution of inflammation.
在发展中社区，肠道感染与体重增加不佳和线性生长衰竭有关。先前的转化动物模型主要关注体重增加，而对线性生长衰竭的关键因素缺乏研究。我们假设，用鼠柠檬酸杆菌感染小鼠肠道会导致与全身炎症和胰岛素样生长因子-1（IGF-1）血清水平降低相关的线性生长衰竭。我们评估了4组在出生后第28天感染或假感染的小鼠：未感染对照组、野生型鼠柠檬酸杆菌感染组、部分减毒鼠柠檬酸杆菌感染组（缺失3个参与定植的丝氨酸蛋白酶基因）和配对喂养组（给予野生型鼠柠檬酸杆菌组每天消耗的食物量）。相对于未感染组，感染野生型鼠柠檬酸杆菌的小鼠表现出食物摄入量降低、体重减轻、线性生长衰竭、白细胞介素-6和肿瘤坏死因子-α水平升高以及IGF-1水平降低的时间相关性。然而，相对于配对喂养组，鼠柠檬酸杆菌感染组仅在线性生长和全身炎症细胞因子方面存在显著差异。在感染后第15 - 20天之间，感染组全身炎症得到缓解。在第16 - 20天之间，野生型鼠柠檬酸杆菌组和配对喂养组均表现出快速的线性生长速度，超过未感染组和突变型鼠柠檬酸杆菌组；在此期间，IGF-1水平升高至与未感染组相当。我们提出这是一个为研究与肠道炎症相关的追赶生长机制提供重要机会的模型。我们得出结论，除了已知的体重减轻影响外，鼠柠檬酸杆菌感染还会导致线性生长衰竭，这可能与全身炎症和低水平的IGF-1有关，炎症消退后线性生长会出现追赶。
