Monocyte regulation by gut microbial signals

The gut microbiota constitutively produce and secrete microbial products/metabolites in the bloodstream that regulate the immune profile of monocytes at extraintestinal tissues.Gut microbial signals can modulate monocyte homeostasis at multiple levels, influencing their production in the bone marrow, their survival in the periphery, and their differentiation to macrophages, dendritic cells, and nonclassical monocytes in various microenvironments.Specific microbial signals shape monocyte functions such as phagocytosis, antigen presentation, cytokine production, antimicrobial ability, and trafficking, thus creating pleiotropic, local, or systemic effects.Preclinical studies in mouse models of colitis, cancer, and neurologic diseases demonstrate that microbiome-activated pathways in monocytes can regulate disease activity, supporting a therapeutic role for microbial signals as modulators of monocyte biology. Monocytes are innate immune cells that sense environmental changes and participate in the immunoregulation of autoimmune, neurologic, cardiovascular, and metabolic diseases as well as cancer. Recent studies have suggested that the gut microbiome shapes the biology of monocytes via microbial signals at extraintestinal sites. Interestingly, in chronic diseases, communication between microbial signals and monocytes can either promote or inhibit disease activity, suggesting that some of these pathways can be harnessed for clinical therapies. In this review, we discuss the newer concepts of regulation of monocyte homeostasis and function by gut microbial signals during steady state and inflammation. We also highlight the therapeutic potential of microbial signal-based approaches for modulation in the context of various diseases.