Oxidative Stress by H₂O₂ as a Potential Inductor in the Switch from Commensal to Pathogen in Oncogenic Bacterium <i>Fusobacterium nucleatum</i>

Background: <i>Fusobacterium nucleatum</i> is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in tumor progression and resistance to chemotherapy. The mechanism by which it transforms from a commensal to a pathogen remains unknown. For this reason, we investigated the role of oxidative status as an initiatory factor in changing the bacterium’s pathogenicity profile. Methods: A clinical strain of <i>F. nucleatum</i> subsp. <i>animalis</i> biofilm was exposed to different oxidative stress levels through varying subinhibitory amounts of H₂O₂. Subsequently, we investigated the bacterium’s behavior in vitro by infecting the HT-29 cell line. We evaluated bacterial colonization, volatile sulfur compounds production, and the infected cell’s oxidative status by analyzing <i>HMOX1</i>, <i>pri-miRNA 155</i>, and <i>146a</i> gene expression. Results: The bacterial colonization rate, dimethyl sulfide production, and <i>pri-miRNA 155</i> levels all increased when stressed bacteria were used, suggesting a predominant pathogenic function of these strains. Conclusions: The response of <i>F. nucleatum</i> to different oxidative conditions could potentially explain the increase in its pathogenic traits and the existence of environmental factors that may trigger the bacterium’s pathogenicity and virulence.