Investigating the role of immnune-related genetic polymorphisms and the oral and gut microbiome composition in the initiation or prevention of automimmunity and type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction. There has been an alarming increase in T1D cases over the last decade in Kuwait, which reflects the presence of both a genetic predisposition as well as a strong environmental influence. Indeed, it is well established that T1D has a multi-factorial pathogenesis involving genetic predisposition, environmental factors, and immune responses. In this first phase study, we aim to identify the genetic and epigenetic risk factors for autoimmunity and T1D in the Kuwaiti population. Specifically, we aim to isolate genomic DNA from T1D cases and matched unaffected family members for whole genome sequencing and Bionano mapping. Depending on the genetic/epigenetic findings, we aim to conduct deep PBMC phenotyping, measure gut cytokines, and sequence the gut and oral microbiome. Moreover, we aim to test for autoantibodies in a large number of children within the population. Results from this study will enable a deeper understanding of the immunopathology of T1D in the Kuwaiti population, and help determine appropriate preventative measures, and/or personalized treatment strategies. In addition, the screening/measurement of autoantibodies in a large number of children will enable early identification of those at risk of progression to T1D, and thus, implementation of preventative strategies.