Systemic instruction of cell-mediated immunity by the intestinal microbiome.

Recent research has shed light on the plethora of mechanisms by which the gastrointestinal commensal microbiome can influence the local immune response in the gut (in particular, the impact of the immune system on epithelial barrier homeostasis and ensuring microbial diversity). However, an area that is much less well explored but of tremendous therapeutic interest is the impact the gut microbiome has on systemic cell-mediated immune responses. In this commentary, we highlight some key studies that are beginning to broadly examine the different mechanisms by which the gastrointestinal microbiome can impact the systemic immune compartment. Specifically, we discuss the effects of the gut microbiome on lymphocyte polarisation and trafficking, tailoring of resident immune cells in the liver, and output of circulating immune cells from the bone marrow. Finally, we explore contexts in which this new understanding of long-range effects of the gut microbiome can have implications, including cancer therapies and vaccination.