Abstract
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.
Highlights
The human intestine houses a tremendous quantity and remarkable diversity of microbes, including bacteria, fungi, viruses, and protozoa
Collectively termed the gut microbiome, form complex ecosystems capable of performing a diverse array of functions that have a wide spectrum of effects on their host’s physiology and health[1,2,3]. Functions include those associated with digestion and nutrient status, but sensing of the gut microbiome is understood to have profound effects on the immune system
Much of this understanding is centred on the effects of the microbiome on the development of local immune responses in the gut, those related to the crucial tasks of maintaining a healthy complex microbial composition and preventing microbes from breaching the simple epithelium[1,4,5] (Figure 1)
Summary
The human intestine houses a tremendous quantity and remarkable diversity of microbes, including bacteria, fungi, viruses, and protozoa. Non-mucosal mononuclear phagocytes have been shown to have altered methylation patterns at key genes associated with type I interferon (IFN) production in GF animals, leading to impaired priming of natural killer cells in the spleen[55] Whether this is mediated by direct effects of microbial ligands on mature immune populations or is due to alterations in haematopoietic development (as discussed ) is unclear. Studies in the 1980s of GF animals, alongside specific pathogen-free animals treated with the antibiotic polymyxin, implicated Gramnegative commensal bacteria in promoting the development of bone marrow granulocyte-monocyte progenitor cells[18] In line with this dependency of granulocyte-monocyte progenitors on the gut microbiota, more recent investigations established deficiencies in differentiated myeloid cell populations in both the spleen and the bone marrow of GF mice[56]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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