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Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response

Dietary fiber & probiotics influence the gut #microbiome & melanoma #immunotherapy response 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.


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https://www.science.org/doi/10.1126/science.aaz7015





Figure. Profiles of gut microbiota in patients with melanoma and associations with outcomes on therapy.

(A) Schema of study design. (B) Box plots comparing the relative abundance of anti–PD-1 response–associated taxa from Gopalakrishnan et al. (4) with a newly recruited cohort (n = 132) of anti–PD-1–treated patients (P = 0.036 and P = 0.018, respectively, for Ruminococcaceae and Faecalibacterium by Wilcoxon rank sum test). Patients included in the prior study were excluded from this analysis. (C) Volcano plot depicting pairwise comparisons of relative abundances of bacterial taxa. The y axis displays the −log10 false discovery rate (FDR)–corrected P value (dashed line, q < 0.1), and the x axis shows the log2 fold change comparing 193 R and 100 NR patients with systemic therapy across the full cohort, including patients from the prior study (by Wilcoxon rank sum test with FDR correction per level). (D) Heatmap of scaled relative abundances [parts per million (PPM)] of bacteria belonging to order Clostridiales and family Ruminococcaceae in pre- and post-FMT samples of anti–PD-1 refractory metastatic melanoma FMT recipients who responded to FMT + anti–PD-1 in Davar et al. (20) [National Center for Biotechnology Information (NCBI) accession no. PRJNA672867]. Number of days from FMT are depicted on the top of each heatmap column, with post-FMT values being the geometric mean days of all post-FMT time points for that patient. The geometric mean of relative abundances of post-FMT samples from each patient were calculated as the single post-FMT mean relative abundance. The exception is patient PT−18−0018, who received two FMTs (denoted by an asterisk). The first post-FMT column for this patient reflects the geometric mean of samples leading up to the second FMT event. (E) Heatmap of scaled relative abundances of bacteria belonging to order Clostridiales and family Ruminococcaceae in pre- and post-FMT samples of anti–PD-1 refractory metastatic melanoma FMT recipients who responded to FMT + anti–PD-1 in Baruch et al. (19) (NCBI accession no. PRJNA678737). Number of days from FMT are depicted on the top of each heatmap column, with post-FMT values being the geometric mean days of all post-FMT time points for that patient. The geometric mean of relative abundances of post-FMT samples from each patient were calculated as the single post-FMT mean relative abundance.


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