Gut microbiota dysbiosis and systemic immune dysfunction in critical ill patients with multidrug-resistant bacterial colonization and infection

BACKGROUND: Antimicrobial resistance (AMR) poses a global health threat, particularly in critically ill patients with multidrug-resistant organism (MDRO) colonization or infection. While evidence suggests the gut microbiota plays a critical role in MDRO colonization and infection, its specific characteristics and the host immune response remain poorly understood. METHODS AND RESULTS: This case-control study compared 88 MDRO-infected patients, 100 MDRO-colonized patients, and 86 healthy controls, using 16S rRNA sequencing and cytokine profiling. MDRO cohorts exhibited profound gut dysbiosis, including reduced gut microbial diversity and distinct community structures, reduced beneficial bacteria (e.g., Bacteroides, Faecalibacterium, Roseburia, Prevotella), and expansion of pathobionts-resident microbes with pathogenic potential (e.g., Enterococcus, Klebsiella, Escherichia-Shigella). Enterotype analysis revealed a shift from a Bacteroides-dominated to one Enterococcus-dominated microbiota in both colonized and infected patients compared to controls. Serum cytokine profiling indicated immune dysfunction in MDRO-associated patients. Correlation analysis showed that beneficial genera were negatively correlated with pro-inflammatory cytokines (IL-1ra, IL-2, IL-7, TNF-α, and IFN-γ) and positively associated with anti-inflammatory markers, while pathobionts exhibited the opposite trend. Several key differential genera, such as Enterococcus and Klebsiella, either individually or in combination, have been identified as key discriminators of MDRO status. Functional predictions through PiCRUSt observed disruptions in carbohydrate and lipid metabolism in the MDRO cohorts. CONCLUSION: Overall, MDRO colonization and infection lead to gut dysbiosis and immune dysfunction, with microbiota-immune interactions playing a crucial role in disease progression, suggesting the gut microbiota as a potential diagnostic and therapeutic target for AMR.