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Changes in the gut microbiota are associated with the etiopathogenesis of complex diseases, such as multiple sclerosis. In this issue of Cell , the international Multiple Sclerosis Microbiome Study consortium deployed a multi-omics approach to profile the composition and function of the gut microbiome in an extensive cohort of MS patients. [ABSTRACT FROM AUTHOR]

Over the last decade, the composition of the gut microbiota has been found to correlate with the outcomes of cancer patients treated with immunotherapy. Accumulating evidence points to the various mechanisms by which intestinal bacteria act on distal tumors and how to harness this complex ecosystem to circumvent primary resistance to immune checkpoint inhibitors. Here, we review the state of the microbiota field in the context of melanoma, the recent breakthroughs in defining microbial modes of action, and how to modulate the microbiota to enhance response to cancer immunotherapy. The host-microbe interaction may be deciphered by the use of "omics" technologies, and will guide patient stratification and the development of microbiota-centered interventions. Efforts needed to advance the field and current gaps of knowledge are also discussed. [ABSTRACT FROM AUTHOR]

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]