Journal
CANCER MEDICINE
Volume 10, Issue 1, Pages 79-86Publisher
WILEY
DOI: 10.1002/cam4.3569
Keywords
dietary supplement; microbiome; probiotics; renal cell carcinoma; targeted therapies; VEGF‐ TKI
Categories
Funding
- Pfizer Inc.
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The study indicates a connection between the gut microbiome and outcomes in mRCC patients, with probiotic supplementation potentially modulating the gut microbiome and affecting the clinical results of VEGF-TKIs. The probiotic yogurt product containing Bifidobacterium successfully increased levels of the bacteria, while certain enriched species like Barnesiella intestinihominis and Akkermansia muciniphila may be associated with clinical benefit.
Studies suggest a link between the gut microbiome and metastatic renal cell carcinoma (mRCC) outcomes, including evidence that mRCC patients possess a lower abundance of Bifidobacterium spp. compared to healthy adults. We sought to assess if a Bifidobacterium-containing yogurt product could modulate the gut microbiome and clinical outcome from vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs). mRCC patients initiating VEGF-TKIs, regardless of the line of therapy, were randomized to probiotic-supplemented (two 4 oz. servings of the probiotic yogurt product daily) or probiotic-restricted arms. Stool samples were collected prior to therapy and at weeks 2, 3, 4, and 12. Microbiome composition was assessed using whole-metagenome sequencing. A total of 20 patients were randomized. Bifidobacterium animalis, the active ingredient of the probiotic supplement, reached detectable levels in all patients in the probiotic-supplemented arm versus two patients in the probiotic-restricted arm. Clinical benefit rate was similar in probiotic-supplemented versus probiotic-restricted arms (70% vs. 80%, p = 0.606). Linear discriminant analysis (LDA) effect size analysis of MetaPhIAn2 abundance data predicted 25 enriched species demonstrating an LDA score >3 in either clinical benefit or no clinical benefit. In patients with clinical benefit (vs. no clinical benefit), Barnesiella intestinihominis and Akkermansia muciniphila were significantly more abundant (p = 7.4 x 10(-6) and p = 5.6 x 10(-3), respectively). This is the first prospective randomized study demonstrating modulation of the gut microbiome with a probiotic in mRCC. Probiotic supplementation successfully increased the Bifidobacterium spp. levels. Analysis of longitudinal stool specimens identified an association between B. intestinihominis, A. muciniphila, and clinical benefit with therapy.
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