Gut microbiota was only considered as a commensal organism that aids in digestion, but recent studies revealed that the microbiome play a critical role in both physiological and pathological immune system. The gut microbiome composition is altered by environmental factors such as diet and hygiene, and the alteration affects immune cells, especially T cells. Advanced genomic techniques in microbiome research defined that specific microbes regulate T cell responses and the pathogenesis of immune-mediated disorders. Here, we review features of specific microbes-T cell crosstalk and relationship between the microbes and immunopathogenesis of diseases including in cancers, autoimmune disorders and allergic inflammations. We also discuss the limitations of current experimental animal models, cutting-edge developments and current challenges to overcome in the field, and the possibility of considering gut microbiome in the development of new drug.