Microbiome changes associated with FMT-mediated clearance of antibiotic-resistant Klebsiella pneumoniae in a murine carriage model.

Carbapenem-resistant Enterobacterales (CRE), including Klebsiella pneumoniae (KP), pose a significant public health threat due to their resistance to last-line antibiotics. Eliminating CRE colonization in asymptomatic carriers is crucial to prevent the spread of resistance, as carriage often serves as a reservoir that enables the transmission of resistant strains to vulnerable populations. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to restore gut microbiome balance and eliminate CRE colonization. However, the mechanisms driving successful decolonization warrant further research. This study investigates the impact of FMT on gut microbiome composition, CRE-KP clearance and host response, in a mouse model of CRE-KP carriage. Mice colonized with CRE-KP, were treated with FMT or left untreated. Shotgun metagenomics of fecal samples were used to monitor changes in microbiome composition and function. FMT resulted in substantial changes in the gut microbiome, with successful clearance correlating with an expansion of commensal bacteria including Bifidobacterium and Lactobacillus species. Notably, a reduction in K. pneumoniae was also observed in some untreated control mice as the microbiome recovered naturally, also associated with Bifidobacterium expansion. Phage profiling revealed distinct viral populations that were associated with successful decolonization. Flow cytometry was employed to quantify bacterial populations bound by immunoglobulins, providing insight into host immune modulation. These findings suggest potential mechanisms for CRE carriage eradication using microbiome targeted therapies. The results emphasize the importance of microbiome resilience in combating antibiotic-resistant infections and suggest that phage-microbiome interactions could play a role in restoring microbial balance.