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 ?-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 ?-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.
Increasing our understanding on how beneficial microbes and their components influence disease prevention or development will have a significant impact on human health. In this proposal, we seek to use a beneficial microorganism as a new strategy to prevent and/or ameliorate symptoms associated with the onset of type 1 diabetes.
