Autoimmune disorders derive from genetic, stochastic, and environmental factors that all together interact in genetically predisposed individuals. The impact of an imbalanced gut microbiome in the pathogenesis of autoimmunity has been suggested by an increasing amount of experimental evidence, both in animal models and humans. Several physiological mechanisms, including the establishment of immune homeostasis, are influenced by commensal microbiota in the gut. An altered microbiota composition produces effects in the gut immune system, including defective tolerance to food antigens, intestinal inflammation, and enhanced gut permeability. In particular, early findings reported differences in the intestinal microbiome of subjects affected by several autoimmune conditions, including prediabetes or overt disease compared to healthy individuals. The present review focuses on microbiota-host homeostasis, its alterations, factors that influence its composition, and putative involvement in the development of autoimmune disorders. In the light of the existing literature, future studies are necessary to clarify the role played by microbiota modifications in the processes that cause enhanced gut permeability and molecular mechanisms responsible for autoimmunity onset.