Impact of Latino ethnicity on the gut microbiome composition of patients with metastatic renal cell cancer (mRCC).

Regina Barragán Carrillo City of Hope Comprehensive Cancer Center, Duarte, CA info_outline Regina Barragán Carrillo, Nazli Dizman, Hedyeh Ebrahimi, Luis A Meza, Paulo Gustavo Bergerot, Tanya B. Dorff, Joann Hsu, Zeynep Busra Zengin, Nicholas Salgia, Alex Chehrazi-Raffle, Abhishek Tripathi, Daniela V. Castro, Benjamin Mercier, Gregory Caporaso, Keehoon Lee, Sumanta Kumar Pal

Authors Regina Barragán Carrillo City of Hope Comprehensive Cancer Center, Duarte, CA info_outline Regina Barragán Carrillo, Nazli Dizman, Hedyeh Ebrahimi, Luis A Meza, Paulo Gustavo Bergerot, Tanya B. Dorff, Joann Hsu, Zeynep Busra Zengin, Nicholas Salgia, Alex Chehrazi-Raffle, Abhishek Tripathi, Daniela V. Castro, Benjamin Mercier, Gregory Caporaso, Keehoon Lee, Sumanta Kumar Pal Organizations City of Hope Comprehensive Cancer Center, Duarte, CA, The University of Texas MD Anderson Cancer Center, Houston, TX, Yale University School of Medicine, New Haven, CT, Oncoclinicas & Co - Medica Scientia Innovation Research (MEDSIR), São Paulo, Brazil, Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, Translational Genomics Institute, Phoenix, AZ, Translational Genomics Research Institute (TGen North), Flagstaff, AZ Abstract Disclosures Research Funding No funding sources reported Background: Latinos with mRCC may have poorer outcomes with frontline immune checkpoint inhibition (ICI) compared to their non-Latino counterparts (Chehrazi-Raffle et al Oncologist 2023). Recent studies have shown that the composition of the gut microbiome can impact outcomes with ICI (Routy et al Science 2018). Therefore, we aimed to investigate the differences in gut microbiome composition between Latino and non-Latino patients (pts) with mRCC. Methods: Stool specimens were prospectively collected in treatment-naïve pts with mRCC. We dichotomized pts into Latino vs non-Latino groups. Pts provided a stool sample (OMNIgene Gut) at baseline. Whole metagenome sequencing was performed on stool specimens collected. Taxonomic profiling was conducted using MetaPhlAn 4. ANCOM-BC analysis was used to identify differences in the relative abundance of bacterial species between groups. Alpha-diversity was evaluated using the Shannon diversity index and Evenness analysis, employing the Kruskal-Wallis test. Beta-diversity was assessed using the Bray-Curtis and Jaccard dissimilarity measures. The ratio of Firmicutes/Bacteroidetes (F/B), a measure of gut dysbiosis, was computed at baseline in the two cohorts. Results: Among 59 pts assessed, 27 and 32 were Latino and non-Latino, respectively. Median age of the cohort was 60 (range, 36-90). Most were male (71%), had clear cell RCC (88%) and had intermediate/poor risk disease (79%). ANCOM-BC analysis showed an enrichment of 14 bacterial species and a depletion in 3 species at baseline in the Latino group (p ≤ 0.05). Three Roseburia spp. were enriched in the Latino pts, namely R. faecis (log-fold change [LFC]: 2.6), R. hominis (LFC: 2.0) and R. inulinivorans (LFC: 1.8). Additionally, Eubacterium rectale was also enriched in the Latino group (LFC: 2.0). In contrast, in non-Latino pts Methylobacterium spp. was enriched (LFC: 1.3). The F/B ratio was higher in the Latino group as compared to the non-Latino group (1.00 vs 0.92). We did not observe any differences in alpha and beta diversity. A detailed analysis of simultaneously collected dietary logs is ongoing. Conclusions: Our examination of the gut microbiota of pts with mRCC revealed significant differences based on ethnicity at baseline. Specifically, the Latino group exhibited an enhancement of Roseburia spp . and E. rectale , species previously linked to favorable outcomes with ICIs, despite a higher F/B ratio (suggesting a greater degree of dysbiosis). Our findings advocate that clinical trials related to the microbiome should potentially account for baseline differences in ethnicity.