The "Three Amigos" lurking behind type 1 diabetes: Hygiene, gut microbiota and viruses

Incidence of type 1 diabetes (T1D) is on the rise and yet, despite decades of research, the exact ethology of the disease still remains a mystery. The autoimmune reaction, which ultimately leads to the destruction of pancreatic beta cells, causing insulin deficiency and T1D, is a result of genetic susceptibility and environmental factors. Precisely, what are these environmental factors? Current popular opinion implies these pathogens, such as viruses, especially human enteroviruses, are a triggering factor. On the other hand, the hygiene hypotheses states in which the increase of autoimmune diseases, such as T1D, can, in fact, be explained by the decrease of infections, and infectious agents, more like viruses, actually serve as a defense mechanism, therefore, protect us from developing certain autoimmune diseases. Additionally, the relationship between the gut microbiota and autoimmune diseases is currently gaining increased interest including relative research now demonstrating how the guts immune system plays a crucial role in the development of autoimmune diseases. This literature review aims to evaluate these three popular suspects: Viral infections, hygiene and gut microbiota, in relation to their potential triggering effect on T1D and their close relationship to one another.