Carbohydrate competition by Enterobacteriaceae enhances colonization resistance to carbapenem-resistant hypervirulent K. pneumoniae

Background: Carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) is a growing public health threat due to its virulence and limited treatment options. While prevalent in hospitals, its presence in livestock, particularly pigs, is poorly understood. The gut microbiome provides colonization resistance, but how it restricts CR-HvKP remains unclear. Results: To further elucidate the colonization resistance mechanisms of the gut microbiota against CR-HvKP, we analyzed stool samples from piglets (L), nursery (N), fattening (F), and sows (PS) using microbiome modeling (Micolo) and competition assays. ST290 K. pneumoniae isolated from PS inhibited CR-HvKP via carbohydrate competition, with a pronounced effect observed for sucrose. Niche-specific supplementation with methyl pyruvate was found to partially alleviate this ecological inhibitory effect. Conclusions: Carbohydrate-based interventions could be explored as potential therapeutic or prophylactic strategies to combat CR-HvKP colonization, thereby potentially improving animal and public health outcomes.