Systemic Immunoregulatory Consequences of Gut Commensal Translocation.

One major determinant of systemic immunity during homeostasis and in certain complex multifactorial diseases (e.g. cancer and autoimmune conditions), is the gut microbiota. These commensals can shape systemic immune responses via translocation of metabolites, microbial cell wall components, and viable microbes. In the last few years, bacterial translocation has revealed itself as playing a key, and potentially causal role in mediating immunomodulatory processes in nongastrointestinal diseases. Moreover, recent observations regarding the presence of complex microbial communities and viable bacteria within gut-distal tissues during homeostasis challenge the current paradigm that healthy mammals are entirely sterile at nonmucosal sites. This review discusses our current understanding of how the gut microbiota orchestrates systemic immunity during noninfectious extraintestinal diseases and homeostasis, focusing on the translocation of viable bacteria to gut-distal sites. A complex tissue microbiome, containing viable bacteria, is present at gut distal sites during homeostasis. A crucial, and potentially causal role of gut bacterial translocation in modulating systemic immunity during extraintestinal diseases, such as autoimmunity and cancer, is emerging. The systemic immunoregulatory consequences of gut bacterial translocation are contextual. Gut-distal tumors and circulatory systems of cancer patients can harbor cancer-type-specific microbial communities of prognostic value. The efficacy of cancer immunotherapy can be strongly associated with gut bacterial translocation. Bacterial translocation can exacerbate the severity of certain autoimmune diseases, potentially through modulating self-reactivity. The aberrant immune response in certain autoimmune diseases may not be attributable to self-antigen reactivity alone, but may be a synergistic effect, including a reaction to gut microbes. [ABSTRACT FROM AUTHOR]