Impact of carbapenem-resistant <i>Klebsiella pneumoniae</i> infection on gut microbiota and host immunity: a case-control study

Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) represents a critical global health threat with limited treatment options. While the gut microbiota is a reservoir for opportunistic pathogens and a regulator of host immunity, the reciprocal impact of systemic CRKP infection on gut microbial ecology and immune responses remains poorly defined. In a prospective case-control study, 38 patients with confirmed CRKP infection and 38 matched hospitalized controls without CRKP were enrolled. Fecal samples underwent 16S rRNA gene sequencing to characterize microbial profiles, and serum cytokine levels were quantified using multiplex immunoassays. CRKP infection was associated with significantly reduced microbial diversity and a distinct shift in community structure, characterized by depletion of beneficial commensals (<i>Bacteroides</i>, <i>Faecalibacterium</i>, <i>Roseburia</i>) and enrichment of pathobionts (<i>Klebsiella</i>, <i>Enterococcus</i>). Enterotype analysis revealed a predominance of a <i>Klebsiella</i>/<i>Enterococcus</i>-dominated enterotype in CRKP patients. Functional predictions indicated impaired carbohydrate and butyrate metabolism alongside increased virulence- and resistance-associated pathways. Systemically, patients exhibited elevated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and chemokines (IP-10, MCP-1, RANTES). Correlation analyses linked opportunistic taxa with heightened inflammatory markers, while beneficial short-chain fatty acid producers showed inverse associations. Systemic CRKP infection is associated with profound gut dysbiosis and a hyper-inflammatory immune response. The strong microbiota-immune correlations suggest that the gut microbiota may serve as a biomarker and a potential therapeutic target for mitigating CRKP-associated immune dysfunction, though the directional relationship (cause vs. consequence) between dysbiosis and CRKP infection remains to be elucidated.IMPORTANCECarbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) is a critical global threat with limited therapeutic options. This study reveals that systemic CRKP infection is associated with profound gut dysbiosis-characterized by loss of beneficial commensals (e.g., <i>Faecalibacterium</i>) and expansion of pathobionts (e.g., <i>Klebsiella</i>, <i>Enterococcus</i>)-as well as a hyperinflammatory immune response. We demonstrate strong correlations between specific microbial taxa and host cytokines, suggesting that the gut microbiome may hold potential as a biomarker and therapeutic target. These findings enhance our understanding of host-microbe interactions in CRKP infection and support the exploration of microbiota-based therapies. However, further studies, including longitudinal and animal models, are needed to clarify whether gut dysbiosis directly influences CRKP outcomes or is a secondary consequence.