Alteration of pro-carcinogenic gut microbiota is associated with clear cell renal cell carcinoma tumorigenesis

Abstract

ABSTRACTIncreasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC. In a pilot case-control study among 30 ccRCC patients and 30 healthy controls, 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on theTCGAdatabase. Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which 9 species, such asDesulfovibrionaceae,were enriched in the RCC group, and 11 species, such as four kinds ofLactobacillus,were less abundant. Concomitantly, serum level of taurine, which was considered to be consumed byDesulfovibrionaceaeand released byLactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such asGabbr1was upregulated in ccRCC patients from our results.IMPORTANCETo our knowledge, few studies investigate the correlation of gut microbiota and ccRCC tumorigenesis. Overall, our sequencing data suggest that changes in the composition of specific gut microbiota, especiallyLactobacillusandDesulfovibrionaceae,may be involved in ccRCC. Numerous serum metabolites, for example, taurine, which were modified in concert with dysregulation of gut microbiota, were associated with metabolic status during ccRCC development. Furthermore, through comparative analysis of clinical indicators, we found that gut dysbiosis could potentially reshape systemic inflammation, which participated in ccRCC tumorigenesis and we performed bioinformatics analysis to draw this conclusion. In Summary, it could be concluded from our study that the reduction of protective bacteriaLactobacillus, proliferation of sulfide-degrading bacteriaDesulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.