Evaluation of safety, tolerability and immunological responses to Lactobacillus johnsonii N6.2 supplementation in adults with Diabetes type 1

虽然基因已被证明是1型糖尿病发展的主要风险因素 (T1D)，微生物区系失调被认为是免疫耐受和启动打破的诱导者 β-细胞自身免疫。益生菌可以用来预防或恢复这种微生物失调。我们 之前在啮齿动物身上进行了一项使用约翰逊氏杆菌N6.2的干预研究，发现 微生物的应用降低了T1D的发生率。将我们的啮齿动物研究转化为 在人类中预防T1D的潜在方法需要在健康个体中进行初步研究。我们 在42名健康个体中进行了一项双盲随机临床试验，这些人没有T1D到T1D的已知危险因素 评估受试者对食用强生乳杆菌N6.2的反应。强生乳杆菌N6.2的给药量为 在成人对照受试者中耐受性良好，表现出对先天和获得性免疫的系统性影响 并导致犬尿氨酸/色氨酸比率下降。这些数据为 强生乳杆菌N6.2在T1D高危人群的预防试验中的安全性和可行性。从长远来看 我们研究的目的是确定服用强生乳杆菌或其成分将预防T1D 起病于儿童。作为朝着这个方向迈出的一步，这项提议的主要目标是测试安全和 成人T1D患者的耐受性。作为这项提议的次要结果，我们假设政府 将在T1D和T1D的背景下促进宿主免疫系统的耐受性倾斜 可保留β细胞功能。我们将通过评估安全性和耐受性来实现这项建议的目标 在患有T1D的成人中检测L.johnsonii N6.2在免疫细胞激活中的作用 成人T1D及其细菌介导的系统信号转导机制的研究 效应器组件。在这项建议完成后，我们将确定L。 Johnsonii N6.2对患有T1D的成年人是安全的，对疾病进展没有不良影响。我们还期待着 已经收集了关于宿主全身反应的细菌效应器的证据。在以下位置获得的数据 该提案将为在高危人群中使用L.johnsonii N6.2进行预防试验提供垫脚石。 T1D。

While genetics has been demonstrated to represent a major risk factor for the development of type 1 diabetes (T1D), microbiota dysbiosis has been suggested as an elicitor of a break in immunological tolerance and initiation of β-cell autoimmunity. Probiotic microorganisms may be used to prevent or restore this dysbiosis. We have previously performed an intervention study using L. johnsonii N6.2 in rodents and found that the administration of the microorganism reduced the incidence of T1D. Translating our rodent studies towards a potential method for T1D prevention in humans required a pilot study in healthy individuals. We conducted a double-blind, randomized clinical trial in 42 healthy individuals with no known risk factors for T1D to evaluate subject responses to the consumption of L. johnsonii N6.2. The administration of L. johnsonii N6.2 was well tolerated in adult control subjects, demonstrated systemic impacts on innate and adaptive immune populations and resulted in a decreased kynurenine/tryptophan ratio. These data provide support for the safety and feasibility of using L. johnsonii N6.2 in prevention trials in subjects at risk for T1D. The long term goal of our research is to determine that the administration of L. johnsonii or its constituents will prevent T1D onset in children. As a step in that direction, the primary goal of this proposal is to test the safety and tolerability in adults with T1D. As a secondary outcome of this proposal, we hypothesize that the administration of L. johnsonii N6.2 will promote tolerogenic skewing of the host immune system in the context of T1D and may preserve β-cell function. We will achieve the goals of this proposal by evaluating the safety and tolerability of L. johnsonii N6.2 in adults with T1D, determining the role of L. johnsonii N6.2 in immune cell activation in adults with T1D and elucidating the mechanism of systemic signal transduction mediated by bacterial effector components. After completion of this proposal, we will have determined that the consumption of L. johnsonii N6.2 is safe for adults with T1D with no adverse effects on disease progression. We further expect to have gathered evidence on the bacterial effectors of systemic responses in the host. The data obtained in the proposal will provide a stepping stone for the use of L. johnsonii N6.2 in prevention trials in subjects at risk for T1D.