Fig. 1: Microbiome-mediated colonization resistance and Klebsiella pneumoniae countermeasures.

Recent studies have highlighted the important role of K. pneumoniae in both infectious and non-infectious diseases, as well as the complex interplay between the gut microbiota and K. pneumoniae colonization. In healthy individuals, the gut microbiota establishes colonization resistance against K. pneumoniae through balanced ecological niches shaped by key commensals, thereby limiting its colonization. The underlying mechanisms include competitive exclusion for nutrients and ecological niches, secretion of antagonistic molecules, and metabolic interference. However, K. pneumoniae can overcome these defenses through intrinsic traits and adaptations, developing multiple strategies to facilitate colonization, such as acquisition of AMR and virulence alterations, unique structural features (e.g., capsule, LPS, and fimbriae), elimination of competitors via T6SS, and metabolic adaptations conferring survival advantages. Future studies should consider the diversity and heterogeneity of K. pneumoniae populations, as well as their adaptability and evolutionary dynamics. Research on colonization resistance may focus on the identification of key commensals and their mechanisms of action, including regulation at the metabolic level. In addition, further investigation is needed into the complex interactions between K. pneumoniae and other gut microbes, as well as host immune evasion strategies. Microbiome-based therapeutic approaches against K. pneumoniae, including commensals, phages, peptides, metabolites, and antibodies, represent promising candidates. AMR antimicrobial resistance, LPS lipopolysaccharide, T6SS the type VI secretion system. Created in BioRender. Yang, Y. (2026) https://BioRender.com/ytu7xgk.