Research in a multitude of biomedical disciplines in the last decade has dramatically increased our awareness of the human body as a “walking ecosystem”. Our gut, oral cavity and skin “habitats” contain a vast number of diverse and distinct communities of microorganisms, collectively known as the “microbiota”. Although it is clear that the microbiota play an important role in host physiology, the maintenance of this mutualistic relationship presents a considerable challenge to the host, i.e. to maintain immune tolerance to “friends” and at the same time effectively mount a defence against “enemies”, i.e. pathogens. For example, together with a breakdown of the barrier function of the intestinal lining, a loss of tolerance to antigens presented by the intestinal microbiota is associated with the chronic inflammatory response to these “symbionts” present in individuals with inflammatory bowel disease (IBD). Because of the microbiota’s importance to both health, and particularly its role in chronic inflammatory disorders such as IBD, my research group has re-dedicated its focus to studying the evolution and genetic basis of interactions between mammalian hosts and their microbiota.