Institutes

Experimental diabetes

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Research associate

Marika Falcone

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Organ-specific autoimmune diseases like Type 1 Diabetes and Multiple Sclerosis result from the interplay between environmental and genetic factors. Recent studies indicate that activation of self-reactive T cells and alterations of immune regulatory pathways may occur at the intestinal level and maybe modulated by environmental factors that modify the gut environment such as diet and microbiota composition. Our goal is to determine whether the intestinal environment plays a role in the pathogenesis of autoimmune diseases such as T1D and MS and to promote immune tolerance in the gut through diet and microbiota modifications for preventions/ treatment of those extraintestinal autoimmune disorders.

Research activity

Type 1 Diabetes (T1D) and Multiple Sclerosis (MS) are autoimmune diseases mediated by self-reactive T cells that destroy insulin-producing b cells and the myelin sheaths. Both genetic and environmental factors are involved in the pathogenesis of T1D and MS but the mechanisms governing the activation of autoimmune T cells are still largely unknown. Growing evidence supports the notion that the gut environment influences the pathogenesis of extra-intestinal autoimmune diseases such as T1D and MS. Specifically, an inflammatory intestinal environment induced by diet and/or commensal microbiota composition can promote activation of autoimmune T cells including islet-specific and myelin-specific self-reactive T lymphocytes within the gut mucosa and/or systemically, thereby triggering T1D or MS pathogenesis. Recently, our group found that humans affected by T1D and MS have alterations of gut mucosal immunity with inflammatory immunological profiles. Moreover, we demonstrated in pre-clinical models of T1D that an inflammatory gut environment promotes activation of self (islet)-reactive T cells by inducing loss of gut barrier continuity and abnormal interaction between immune cells and commensal gut microbiota leading to activation of self(islet)-reactive T cells and autoimmune diabetes.

We are currently investigating in humans and animal models of T1D and MS how gut inflammation, modification of the microbiota composition and intestinal and mucus barrier integrity affect the autoimmune pathogenesis of T1D and MS. Furthermore, we are exploiting the capacity of probiotic and prebiotic therapeutic approaches to modulate T1D pathogenesis in designed clinical trials.