• The Impact of Staphylococcus aureus Gut Colonization on Genome Instability and Inflammatory Bowel Disease (IBD) Pathogenesis: A Narrative Review
  • Arshia Tajik,1 Arshia Amin Attaei,2 Armin Motevalli Jooybari,3 Hiva Danesh,4,*
    1. Department of Medical Laboratory Sciences, TeMS.C., Islamic Azad university, Tehran, Iran
    2. Department of Medical Laboratory Sciences, TeMS.C., Islamic Azad university, Tehran, Iran
    3. Department of Medical Laboratory Sciences, TeMS.C., Islamic Azad university, Tehran, Iran
    4. Department of Medical Laboratory Sciences, TeMS.C., Islamic Azad university, Tehran, Iran


  • Introduction: Staphylococcus aureus (S. aureus) is a highly adaptable and virulent pathogen, historically associated with skin and systemic infections. However, recent evidence highlights its potential role in gastrointestinal disorders, especially inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis. The ability of S. aureus to colonize the gut, disturb microbiota balance, and provoke immune activation suggests a complex role in intestinal health and disease. This narrative review aims to explore the current understanding of how S. aureus gut colonization influences intestinal inflammation, microbial dysbiosis, epithelial genomic instability, and the pathogenesis or exacerbation of IBD. It also differentiates the roles of MRSA and MSSA strains and discusses potential implications for future therapeutic strategies.
  • Methods: A structured search of scientific literature was conducted using databases such as PubMed, Scopus, and Google Scholar. Keywords including “Staphylococcus aureus,” “MRSA,” “gut microbiome,” “IBD,” and “genomic instability” were applied. Peer-reviewed original articles, review papers, and experimental studies from the past ten years were prioritized. Inclusion criteria included relevance to gut colonization, host-pathogen interactions, and intestinal pathology.
  • Results: Staphylococcus aureus demonstrates the ability to colonize and persist in the gastrointestinal tract by adhering to mucosal surfaces, outcompeting commensal flora, and resisting hostile conditions such as bile salts, low pH, and antimicrobial peptides. Once established, virulence factors—particularly α-toxin and phenol-soluble modulins (PSMs)—induce mucosal injury, oxidative stress, and local immune activation. These effects are notably pronounced in methicillin-resistant strains (MRSA), which often exhibit higher virulence factor expression compared to methicillin-sensitive strains (MSSA), especially in epidemic clones. Colonization by S. aureus significantly disrupts the gut microbiome, compromising epithelial barrier integrity and potentially enabling systemic translocation or distant mucosal damage, including to the blood–brain barrier. Furthermore, interactions with host immune receptors, such as Toll-like receptors, activate NF-κB signaling pathways, promoting the secretion of pro-inflammatory cytokines including IL-6, TNF-α, and IFN-γ—hallmarks of chronic intestinal inflammation. Importantly, S. aureus-induced reactive oxygen species (ROS) contribute to genotoxic stress by generating DNA double-strand breaks and oxidative lesions such as 8-oxo-guanine. Some strains additionally suppress host DNA repair mechanisms, elevating genomic instability and mutational burden in intestinal epithelial cells—mechanistic pathways linked to inflammatory bowel disease (IBD) pathogenesis and possibly colorectal carcinogenesis. Clinical and experimental evidence indicates an increased prevalence of S. aureus colonization in patients with IBD. Although causality has not been definitively established, current data support its contributory role in disease exacerbation and immune dysregulation.
  • Conclusion: S. aureus may serve as a hidden aggravating factor in IBD pathogenesis by promoting chronic inflammation, microbiota disruption, and epithelial genomic damage. While definitive clinical evidence is still lacking, the convergence of microbiological, immunological, and genotoxic mechanisms underscores the importance of further research. Understanding these pathways could inform future interventions to prevent or treat inflammation-related gastrointestinal disorders. As our understanding deepens, the gut colonization of S. aureus may emerge not only as a biomarker of disease severity but also as a novel therapeutic target in IBD.
  • Keywords: Staphylococcus aureus, MRSA, gut microbiota, IBD, DNA damage