Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response
Study found that melanoma patients reporting high fiber (prebiotic) consumption had better response to checkpoint inhibitor immunotherapy than patients reporting a low-fiber diet.
Another benefit of dietary fiber
The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al. add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response. —PNK
Abstract
Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.
Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy (1), and the influence of the gut microbiome on therapeutic response has now been demonstrated in numerous human cohorts and in preclinical models (2–7). The human gut microbiome is itself shaped by a wide variety of environmental exposures, including diet (8, 9) and medication use (10–13), with host genetics accounting for <10% of variation (14). However, whether factors such as dietary fiber intake and the use of commercially available probiotics affect immunotherapy responses in cancer patients remains unclear.
To help address this, we profiled the gut (fecal) microbiome and assessed clinicopathologic features and outcomes in a large cohort of melanoma patients (n = 438; Fig. 1A and fig. S1). The majority of these patients were receiving systemic therapy for metastatic melanoma (n = 321), and responses to treatment were assessed with radiographic imaging in those with evaluable treatment responses (n = 293), classifying patients as either responders [(R) complete or partial response or stable disease ≥6 months; n = 193] or nonresponders [(NR) stable disease <6 months or progressive disease; n = 100] using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (15). The majority of patients were treated with ICB (87%), most commonly anti–programmed cell death 1 (anti–PD-1) therapy (Fig. 1A, fig. S1, and table S1). Patients initiating therapy with ICB were asked to co-enroll onto a lifestyle survey protocol, which included baseline assessments of dietary habits and use of probiotic supplements within the past month (n = 158; Fig. 1A, fig. S1, and table S1) (16, 17).
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https://www.science.org/doi/10.1126/science.aaz7015
