AbstractThe gut microbiotaParvimonas micrahas been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential ofP. micraand its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For everyP. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically withP. micraat an MOI of 100:1 (bacteria: cells) for 2 h. We found thatP. micraincreased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5,IL-8,CCL20, andCSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed thatP. micraaffects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin–proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial–mesenchymal transition (EMT)-markers were expressed in HT-29 infected withP. micra. Overall, the present study elucidated exacerbated oncogenic properties ofP. micrain HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.