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Role of gut extracellular vesicles in the development of diabetic peripheral neuropathy
Peripheral neuropathy is one of the major complications of diabetes that greatly contributes to morbidity and mortality. Currently, there is no effective treatment for diabetic peripheral neuropathy (DPN). At early stage, diabetes affects the intestinal microbial composition that drives the metabolic syndrome. However, how gut dysbiosis contributes to the diabetic complication including DPN has not been investigated. Extracellular vesicles (EVs) mediate intercellular communication and bacterial EVs retain bacterial genetic and biomaterials that are associated with many disorders. Recent studies show that among many biological affects, gut microbiota-derived extracellular vesicles (gut-EVs) participate in immune signaling pathways, host metabolic homeostasis, and bacterial metabolite production. However, the impact of gut-EVs on DPN is unknown. In the present study, we propose to investigate whether gut-EVs contribute to the development of DPN, whereas probiotic-EVs alleviate DPN in diabetic mice with peripheral neuropathy and its underlying molecular mechanisms. These studies will not only significantly expand our understanding of molecular mechanism underlying gut microbiota-peripheral nerve communication and induction of DPN, but also provide a novel role of microbiota-derived EVs as a new potential therapeutic strategy in the treatment of DPN and other neurological disorders.

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