The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared to non-CRC controls. In this study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 hr. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 hr post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, CSF2) was also significantlyinduced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated; 214 down-regulated proteins). Upregulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin-proteasome pathway in CRC carcinogenesis; whereas downregulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial-mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, this study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, upregulation of ubiquitin-proteasome pathway (UPPs) and activation of EMT pathways.

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