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

通过使用遗传工具，研究人员已经确定了天然存在的细菌，这些细菌似乎消耗乳酸，从而在高淀粉条件下维持动物的胃肠道平衡。这些细菌可能提供“正确”的微生物参与者，以防止或尽量减少马和反刍牲畜的板膜炎。初步数据证实，体外系统模拟了淀粉诱导的板膜炎期间马肠道中细菌代谢物的波动，并能够随时间跟踪细菌种群。一组细菌，绒毛菌科，显示出利用乳酸的益生菌的希望，乳酸在淀粉诱导过程中增加，被认为与导致板炎的代谢级联有关。研究小组已经分离出了具有利用乳酸和耐低pH值和储存条件潜力的Veillonellaceae菌株。该提案支持进一步的工作：a)使用体外系统证明分离菌株，单独和混合，可以预防或改善马和牛胃肠道样品中淀粉引起的酸中毒（板炎）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；C)确定有效菌株的稳健性，即在选择培养基上的生长速度、氧耐受性和冻干稳定性（干燥耐受性）。这个项目的预期结果是一个原型配方，可以在动物模型上进行乳酸性酸中毒试验，也可以在患有慢性牧场板炎的志愿者临床病例中进行试验。对乳酸酸中毒和板层炎背后的微生物动力学的新认识可能会导致更明智的健康模型，改进饲料配方和管理实践，并为受影响的马开发益生菌治疗方法，可用于预防和/或治疗每年影响数百万马的疾病。这些细菌可以加入动物饲料中，以防止引发板层炎的发酵事件，这可能有助于通过减少牛中板层炎的病例数量来提高牛肉和乳制品的产量，并降低马主的医疗费用。

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.