The intervention of B. longum metabolites in Fnevs' carcinogenic capacity: A potential double-edged sword

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Fusobacterium nucleatum and its metabolites are effective biological targets for colon cancer promotion. Probiotics such as Bifidobacterium can block the occurrence and development of CRC by regulating the host intestinal mucosal immunity, eliminating carcinogens, and interfering with tumor cell proliferation and apoptosis. We selected six Bifidobacterium species to explore the inhibitory effect of their cell-free supernatant (CFS) on Fusobacterium nucleatum, and screened the best functional strain Bifidobacterium longum (B. longum) to explore its intervention effect on Fnevs infection of CRC cells. In the genus Bifidobacterium, B. longum-CFS can effectively inhibit the growth and membrane formation of Fusobacterium nucleatum. The metabolites of B. longum can inhibit the proliferation, migration and invasion of Fnevs-infected CRC cells. However, the transcriptomic analysis of Fnevs-infected CRC cells treated with Bl-CFS revealed that Bl-CFS exerted inhibitory effects on the expression of specific oncogenes (e.g., Myc, IL16, KCNN2, ACSBG1, Pum1, MET, NR5A2), while simultaneously promoting the expression of other oncogenes. This modulation potentially enhances the proliferation, epithelial-mesenchymal transition (EMT), stemness properties and other characteristics associated with CRC cells. Metabolomics also showed that Bl-CFS altered organic acid and lipid metabolism in Fnevs-infected CRC cells, and switched energy supply from aerobic glucose metabolism (TCA cycle) to anaerobic glycolysis, which increased the malignancy potential of CRC cells. The observed outcome may be attributed to the presence of both probiotics and toxic substances in the metabolites derived from Bifidobacterium longum. Therefore, this study concludes that the anti-colorectal cancer (CRC) effect of natural metabolites derived from Bifidobacterium longum is limited. Future investigations should focus on refining these natural substances and optimizing their composition ratios to extract their essence while eliminating impurities, thereby obtaining anticancer biologics with exceptional and consistent efficacy.