Friends and foes: impact of bacteria on genome stability

Bacteria, present in normal conditions in the microbiome or during infections, exert profound effects on genome stability, with both genotoxic and genoprotective consequences. Certain pathogenic bacteria, such as Escherichia coli (colibactin-producing strains), Helicobacter pylori, Fusobacterium nucleatum, and Campylobacter jejuni, induce DNA damage and are implicated in cancer development through direct toxin production, chronic inflammation, immune modulation, and disruption of host cell signaling. Genotoxins such as colibactin, the cytolethal distending toxin, and the typhoid toxin induce DNA double-strand breaks, chromosomal instability, and impair DNA repair pathways, contributing to carcinogenesis. These effects occur upon gastrointestinal, urogenital, systemic (sepsis), and neurological (meningitis) infections, in both humans and animals. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, play a protective role by reducing oxidative DNA damage, modulating immune responses, and enhancing DNA repair. Their beneficial actions are partly mediated by metabolites such as short-chain fatty acids (e.g. butyrate), which influence gene regulation, apoptosis, and mucosal health. Probiotic bacteria can mitigate the genotoxic effects of dietary and bacterial toxins, offering a potential preventive strategy against genome instability and cancer. This review highlights the dualistic nature of bacterial influence on host genome integrity and underscores the importance of maintaining microbial balance.