Klebsiella pneumoniae in inflammatory bowel disease and rectal cancer: from gut inflammation to a potential driver of carcinogenesis.

The gut microbiota is a critical modulator of intestinal inflammation and colorectal cancer (CRC), yet the specific microbial drivers that bridge inflammatory bowel disease (IBD) to rectal carcinogenesis remain poorly defined. Klebsiella pneumoniae (K. pneumoniae) has recently emerged as a compelling candidate at this nexus; however, several critical questions remain unresolved: (i) whether K. pneumoniae colonization is a cause or a consequence of rectal carcinogenesis; (ii) how strain level heterogeneity determines pathogenic versus commensal outcomes; and (iii) which rectal microenvironmental factors selectively amplify its carcinogenic potential. Moreover, the potential utility of persistent colonization with carcinogenic K. pneumoniae strains as a predictive biomarker and target for chemoprevention warrants further investigation. This review systematically addresses these questions by integrating findings from microbial ecology, virulence factor biology, host immunology, and oncogenic signaling. We dissect the dual role of K. pneumoniae along the inflammation cancer axis, focusing on its capacity to promote T helper 17 (Th17) driven inflammation, disrupt the epithelial barrier, and directly alkylate host DNA via colibactin-like genotoxins. We propose a mechanistic framework in which chronic K. pneumoniae colonization acts as a bridge between IBD activity and rectal tumorigenesis, and we critically evaluate the potential of phage therapy, virulence inhibitors, and microbiome-based biomarkers to intercept this process. Finally, we highlight key knowledge gaps and outline future directions required to establish causality and translate these insights into clinical strategies for IBD associated rectal cancer prevention.