The global spread of antibiotic-resistant pathogens threatens to increase the mortality of cancer patients significantly. We propose that chemotherapy contributes to the emergence of antibiotic-resistant bacteria within the gut and, in combination with antibiotics, drives pathogen overgrowth and translocation into the bloodstream. In our model, these processes are mediated by the effects of chemotherapy on bacterial mutagenesis and horizontal gene transfer, the disruption of commensal gut microbiology, and alterations to host physiology. Clinically, this model manifests as a cycle of recurrent sepsis, with each episode involving ever more resistant organisms and requiring increasingly broad-spectrum antimicrobial therapy. Therapies that restore the gut microbiota following chemotherapy or antibiotics could provide a means to break this cycle of infection and treatment failure.
Trends
Changes in gut microbiota are significant precursors to sepsis in cancer patients.
Chemotherapy is damaging to the commensal gut microbiota.
Chemotherapy is likely to produce de novo antimicrobial resistance in gut microbiota by activating the bacterial SOS system.
Microbiome-based therapeutic interventions may be able to correct dysbiosis and prevent carriage of antimicrobial-resistant pathogens.