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  • Presentation

The Microbiota’s Role in Autoimmunity, Melanoma Immunotherapy, and Diet

Description

The talk explains that the microbiota includes bacteria, fungi, viruses, and other microbes living at barrier sites such as the skin, gut, mouth, and lungs, and that modern sequencing has made it possible to study them in detail. The speaker describes how microbes shape immunity from birth onward, how medications and lifestyle alter the microbiome, and how disruption of barriers or immune training can contribute to disease. Two main mechanisms linking microbes to autoimmunity are highlighted: molecular mimicry, where microbial proteins resemble human proteins and trigger cross-reactive antibodies or T cells, and bacterial translocation, where microbes cross damaged barriers and drive inflammation. Lupus is used as the main example, with several microbes and dietary factors implicated, and early studies suggesting that antibiotics, diet changes, vaccines, or fecal transplants may reduce disease activity in mice and perhaps humans. The talk then contrasts this with melanoma immunotherapy, where certain gut microbes appear to improve response to immune checkpoint inhibitors, while recent antibiotics or proton pump inhibitors are associated with worse survival. Diet also matters: high-fiber diets may improve outcomes, probiotics are not clearly beneficial and may even be harmful in some contexts, and exercise and certain dietary components can shift the microbiome in ways that influence immunity. The overall message is that the immune system and microbiota are tightly linked, and that healthy plant-based, fiber-rich diets are generally favored, while overly restrictive or “immune-boosting” supplements should be approached cautiously.

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Conclusions

  • The microbiome is tightly linked to immune function, so disruptions in microbial balance can contribute to autoimmune disease while beneficially enhancing anti-tumor immunity in some settings.
  • In lupus and related autoimmunity, microbes may drive disease through both molecular mimicry and bacterial translocation across impaired barriers.
  • Specific commensal or translocating bacteria can provoke autoantibodies and inflammatory pathways in lupus, and reducing or reshaping these microbes can improve disease in animal models and may help in early human studies.
  • Fecal microbiota transplantation shows promise as a way to rebalance the microbiome and reduce autoimmune activity, but the evidence is still early and donor selection remains unresolved.
  • In melanoma, the gut microbiome appears to influence response to immune checkpoint inhibitors, with some microbial patterns associated with better survival and tumor control.
  • High-fiber diets are associated with better melanoma immunotherapy outcomes, whereas probiotics have not shown consistent benefit and may even be unhelpful in some contexts.
  • Recent antibiotic or proton pump inhibitor exposure around the start of immunotherapy is associated with worse melanoma survival, likely by disrupting helpful microbiota.
  • Fecal transplant before anti-PD therapy may improve response and survival in melanoma, but current evidence is still from small early-phase studies.
  • Exercise and certain diet-derived microbial metabolites may enhance anti-cancer immunity by training T cells and supporting tumor-killing responses.
  • Restrictive dietary patterns such as short-term fasting, caloric restriction, ketosis, or plant-based diets can reduce inflammation, but they are not universal cures and their effects likely depend on the disease context.
  • Healthy plant-based, fiber-rich foods are the most defensible general dietary recommendation because they support beneficial microbes and generate short-chain fatty acids that can suppress inflammatory pathways.
  • Overall, the presenter concludes that microbiome-targeted strategies are promising in both autoimmunity and cancer, but most patient-specific dietary or probiotic claims currently exceed the available evidence.
  • Gopalakrishnan et al., Science 2021.
  • Control of immunity via nutritional interventions. Collins N, Belkaid Y. Immunity. 2022 Feb 8;55(2):210-223. doi: 10.1016/j.immuni.2022.01.004.#10.1016/j.immuni.2022.01.004