The tissue micro environment or milieu consists of a highly dynamic population of cellular and non-cellular components which constitute a complex regulatory network aimed at maintaining the organ homeostasis. In the modern medicine the discovery of miRNAs is undoubtedly a promising field of research and they are essential in orchestrating immune system logic and their release in the gut micro milieu can directly affect bacterial gene expression. Here, we briefly review the role of microRNAs, focuses on their role on immune system components in physiological and pathophysiological gut micro milieu.