Randomized trial assessing impact of probiotic supplementation on gut microbiome and clinical outcome from targeted therapy in metastatic renal cell carcinoma.

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  • Additional Information
    • Source:
      Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-
    • Subject Terms:
      Gastrointestinal Microbiome*; Antineoplastic Agents/*therapeutic use ; Bacteria/*growth & development ; Carcinoma, Renal Cell/*drug therapy ; Intestines/*microbiology ; Kidney Neoplasms/*drug therapy ; Probiotics/*therapeutic use ; Yogurt/*microbiology; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/adverse effects ; California ; Carcinoma, Renal Cell/microbiology ; Carcinoma, Renal Cell/secondary ; Feces/microbiology ; Female ; Host-Pathogen Interactions ; Humans ; Kidney Neoplasms/microbiology ; Kidney Neoplasms/pathology ; Male ; Middle Aged ; Molecular Targeted Therapy ; Probiotics/adverse effects ; Prospective Studies ; Time Factors ; Treatment Outcome
    • Abstract:
      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 × 10 -6 and p = 5.6 × 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. Trial Registration: NCT02944617.
      (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
    • References:
      Genet Mol Res. 2017 Mar 22;16(1):. (PMID: 28340269)
      Science. 2018 Feb 16;359(6377):801-806. (PMID: 29301960)
      Ann Oncol. 2018 Jun 1;29(6):1437-1444. (PMID: 29617710)
      Bioinformatics. 2014 Aug 1;30(15):2114-20. (PMID: 24695404)
      Immunity. 2016 Oct 18;45(4):931-943. (PMID: 27717798)
      Science. 2011 Oct 7;334(6052):105-8. (PMID: 21885731)
      N Engl J Med. 2018 Jun 21;378(25):e34. (PMID: 29897866)
      Microbiome. 2018 Nov 8;6(1):201. (PMID: 30409177)
      Br J Nutr. 2015 Jan;113 Suppl:S1-5. (PMID: 25498959)
      Clin Cancer Res. 2015 Dec 1;21(23):5286-93. (PMID: 26152743)
      Nat Methods. 2012 Jun 10;9(8):811-4. (PMID: 22688413)
      Acta Gastroenterol Latinoam. 2008 Mar;38(1):16-25. (PMID: 18533353)
      Nutrients. 2019 Nov 22;11(12):. (PMID: 31766592)
      Science. 2018 Jan 5;359(6371):104-108. (PMID: 29302014)
      Science. 2018 Jan 5;359(6371):97-103. (PMID: 29097493)
      Ann Surg Oncol. 2010 Jun;17(6):1471-4. (PMID: 20180029)
      Nat Methods. 2015 Oct;12(10):902-3. (PMID: 26418763)
      Science. 2018 Jan 5;359(6371):91-97. (PMID: 29097494)
      N Engl J Med. 2017 Jan 26;376(4):354-366. (PMID: 28121507)
      Neoplasia. 2017 Oct;19(10):848-855. (PMID: 28923537)
      Nat Med. 2018 Jun;24(6):749-757. (PMID: 29867230)
    • Contributed Indexing:
      Keywords: VEGF-TKI; dietary supplement; microbiome; probiotics; renal cell carcinoma; targeted therapies
    • Molecular Sequence:
      ClinicalTrials.gov NCT02944617
    • Accession Number:
      0 (Antineoplastic Agents)
    • Publication Date:
      Date Created: 20201102 Date Completed: 20210720 Latest Revision: 20210720
    • Publication Date:
      20231215
    • Accession Number:
      PMC7826461
    • Accession Number:
      10.1002/cam4.3569
    • Accession Number:
      33135866