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.
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This research was funded by National Institutes of Health HD060739-01 (MDD), AI-033096 (JPN) and DK084045 (JLF) and the Bill and Melinda Gates Foundation OPP1137923 (MDD and JPN).
DeBoer, Mark D.; Vijayakumar, Vidhya; Gong, Meiqing; Fowlkes, John L.; Smith, Rachel M.; Ruiz-Perez, Fernando; and Nataro, James P., "Mice with Infectious Colitis Exhibit Linear Growth Failure and Subsequent Catch-Up Growth Related to Systemic Inflammation and IGF-1" (2017). Barnstable Brown Diabetes Center Faculty Publications. 7.