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

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

The Gut Microbiota Activates AhR Through the Tryptophan Metabolite Kyn to Mediate Renal Cell Carcinoma Metastasis

“…Fecal microorganisms and metabolites are often affected by diet ( 34 ). In this study, the subjects were not given a standardized diet like other studies ( 3 ) but kept the original eating habits, which is the limitation of this study. However, non-invasive research can be overcome by expanding the sample size.…”

“…Studies have shown a link between the gut microbiota and metastatic RCC (mRCC). Evidence showed that RCC patients have a lower abundance of bifidobacteria , compared with healthy adults ( 3 ). However, it needs experimental verification about whether there is a connection between the gut microbiota and RCC needs to.…”

The interaction of Akkermansia muciniphila with host-derived substances, bacteria and diets

“…In a human study, the administration of L. rhamnosus HN001 and B. longum BB536 increases the abundance of A. muciniphila (Toscano et al 2017). Dizman et al demonstrated that fermented milk with B. animalis could improve the abundance of A. muciniphila in metastatic renal cell carcinoma patients (Dizman et al 2021). These species may interact with A. muciniphila although the interaction mechanism is unknown.…”

Nutritional Interventions Targeting Gut Microbiota during Cancer Therapies

“…An interesting randomized controlled trial assessed whether a Bifidobacterium -containing yogurt product could modulate the gut microbiome and clinical outcomes of metastatic renal cell carcinoma (mRCC) patients initiating vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) [ 95 ]. They randomized patients into the probiotic-supplemented group (receiving two servings of 120g probiotic yogurt product daily) or the probiotic-restricted control group.…”

“…Additionally, in patients with clinical benefit (i.e., response of either complete/partial response or stable disease for over 6 months), Barnesiella intestinihominis and Akkermansia muciniphila were significantly more abundant compared with patients with no clinical benefit. [ 95 ]. This is the first study prospectively assessing the impact of fermented food on clinical outcomes in cancer patients undergoing chemotherapy.…”