I-Corps: Probiotics to Prevent Metabolic Changes Associated with Starch Induced Laminitis

通过使用遗传工具，研究人员已经识别出似乎消耗乳酸的自然产生的细菌，从而在高淀粉条件下维持动物的胃肠平衡。这些细菌可能提供“正确的”微生物参与者，以防止或最大限度地减少马和反刍动物的板层炎程度。初步数据证实，体外系统模拟了淀粉诱导的椎板炎期间马肠道细菌代谢物的波动，并能够随着时间的推移跟踪细菌种群。其中一组细菌--韦洛纳科细菌--作为一种益生菌显示出利用乳酸的能力。乳酸在淀粉诱导期间会增加，被认为与导致椎板炎的代谢级联有关。该研究小组已经分离出具有利用乳酸和耐低pH值和储存条件的潜力的韦洛纳科菌株。这项建议支持进一步的工作，以便：a)利用体外系统证明分离的菌株，无论是单独的还是在混合物中，都可以防止或改善马和牛的胃肠道样本中淀粉引起的酸中毒(板层炎)的微生物变化特征；b)进行剂量滴定研究，以确定菌株或混合物的有效浓度；以及c)确定有效菌株的稳健性，即在选择介质上的生长速度、耐氧性和冷冻干燥稳定性(耐干性)。该项目的预期结果是一个原型配方，准备在诱导性乳酸酸中毒的动物模型或一组患有慢性牧场板炎的志愿者临床病例上进行测试。对乳酸酸中毒和板层炎背后的微生物动力学的新理解可能会导致更好地了解健康模式，改进饲料配方和管理实践，并开发一种针对受影响马的益生菌治疗方法，可用于预防和/或治疗每年影响数百万匹马的疾病。这些细菌可以被加入到动物饲料中，以防止引发板层炎的发酵事件，这可能有助于通过减少牛的板层炎病例数量来提高牛肉和乳制品产量，并降低马主的医疗成本。

Through the use of genetic tools, researchers have identified naturally occurring bacteria that appear to consume lactic acid thus maintaining gastro-intestinal balance in animals under high starch conditions. These bacteria may provide the "right" microbial participants to prevent or minimize the extent of laminitis in horses and ruminant livestock. Preliminary data verifies that the in vitro system models fluctuations in bacterial metabolites seen in the horse gut during starch-induced laminitis and enables the tracking of bacterial populations over time. One group of bacteria, the Veillonellaceae, show promise as a probiotic for the ability to utilize lactic acid, which is known to increase during starch induction, and thought to be implicated in the metabolic cascade leading to laminitis. The research team has isolated strains of Veillonellaceae with potential to utilize lactate and withstand low pH and storage conditions. This proposal supports further work to: a) use the in vitro system to demonstrate that isolated strains, individually and in mixtures, can prevent or ameliorate microbial changes characteristic of starch induced acidosis (laminitis) in horse and cattle GI samples; b) conduct dose titration studies to determine effective concentrations of strains or mixtures and; c) determine the robustness of effective strains, namely growth rate on selective media, oxygen tolerance, and lyophilization stability (desiccation tolerance). The anticipated outcome for this project is a prototype formulation ready for testing on either an animal model of induced lactic acidosis or a cohort of volunteer clinical cases with chronic pasture laminitis.A new understanding of the microbial dynamics underlying lactic acidosis and laminitis may lead to better informed models of health, improved feed formulations and management practices, and the development of a probiotic treatment for affected horses that can be used to prevent and/or treat a condition affecting millions of horses annually. These bacteria can be incorporated into animal feed to protect from the fermentative events that trigger laminitis and this could potentially help improve beef and dairy production by decreasing the number of cases of laminitis among cattle, as well as reducing medical costs for horse owners.