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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]

Abstract: Also physical exercise in general is accepted to be protective, acute and strenuous exercise has been shown to induce oxidative stress. Enhanced formation of free radicals leads to oxidation of macromolecules and to DNA damage. On the other hand ultra-endurance events which require strenuous exercise are very popular and the number of participants is continuously increasing worldwide. Since only few data exists on Ironman triathletes, who are prototypes of ultra-endurance athletes, this study was aimed at assessing the risk of oxidative stress and DNA damage after finishing a triathlon and to predict a possible health risk. Blood samples of 42 male athletes were taken 2 days before, within 20min after the race, 1, 5 and 19 days post-race. Oxidative stress marker increased only moderately after the race and returned to baseline after 5 days. Marker of DNA damage measured by the SCGE assay with and without restriction enzymes as well as by the sister chromatid exchange assay did either show no change or deceased within the first day after the race. Due to intake during the race and the release by the cells plasma concentrations of vitamin C and α-tocopherol increased after the event and returned to baseline 1 day after. This study indicates that despite a temporary increase in some oxidative stress markers, there is no persistent oxidative stress and no DNA damage in response to an Ironman triathlon in trained athletes, mainly due to an appropriate antioxidant intake and general protective alterations in the antioxidant defence system. [ABSTRACT FROM AUTHOR]