Transcriptome profiling of human colonic cells exposed to the gut pathobiontStreptococcus gallolyticussubsp.gallolyticus

Abstract

AbstractStreptococcus gallolyticus sp. gallolyticus (SGG)is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher the contribution ofSGGin tumor initiation and/or acceleration respectively, a global transcriptome was performed in normal colonic cells (FHC) and in tumoral colonic cells (HT29). To identifySGG-specific alterations, we chose the phylogenetically closest relative,Streptococcus gallolyticussubsp.macedonicus(SGM)as the control bacterium. We show thatSGM,a bacterium generally considered as safe, did not induce any transcriptional changes on the two human colonic cells. The transcriptional reprogramming induced bySGGwas significantly different in FHC and HT29 cells, with most of the up- and down-regulated genes associated with cancer disease. Top up-regulated genes related to cancer were: (i)IL-20, CLK1, SORBS2, ERG1, PIM1, SNORD3Afor normal FHC cells and (ii)TSLP, BHLHA15, LAMP3, ZNF27B, KRT17, ATF3for cancerous HT29 cells.SGGinduces much stronger transcriptional changes in cancerous than in normal colonic cells (2,090vs128 genes being affected, respectively). Gene set enrichment analysis reveals thatSGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest thatSGGinduces a pro-tumoral shift in human colonic cells, particularly in transformed cells potentially accelerating tumor development in the colon.