ECCMID 2019 - Cancer chemotherapy drives antimicrobial resistance by disrupting the gut microbiome

  • Jackie Johnson
  • Conference Reports
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For this study, investigators led by Geraint Rogers hypothesised that chemotherapy could alter the composition of the commensal intestinal microbiota and give rise to de novo antibiotic resistance. Looking at 16 patients before and after chemotherapy, they observed an expansion of Enterobacteriaceae. However, there were no other significant changes in the microbiome structure. They found a significantly increased carriage of transmissible efflux pump-related resistance genes, oqxB and MuxB, in addition to a significant increase in drug-resistant bacterial colonies.

Cytotoxic chemotherapies cause double-strand and single-strand DNA breaks, which triggers the SOS response in bacteria. The SOS response drives de novo mutations, resulting in multidrug-resistant strains, Rogers noted. Mitomycin C, a chemotherapeutic drug in the alkylating agent class, has been shown to drastically alter E. coli morphology after treatment.  Similar results have been observed after treatment with cisplatin, a commonly used chemotherapy that gives rise to GG and AG intra-strand crosslinks.

Severe sepsis is involved in at least 5% of all cancer hospitalizations and can be caused by neutropenia due to cytotoxic chemotherapy1,2. The current treatment for sepsis centers on rapid, empirical, broad-spectrum antibiotics; however, preclinical models have shown that antibiotic disruption of the gut microbiome increases the risk of blood stream infections by the expansion of multidrug-resistant E. coli. Rogers 3 emphasized that chemotherapy precipitates dysbiosis, allowing pathogen proliferation. Antibiotics then act as a powerful selector for resistant bacteria, which damages the intestinal barrier and host defenses.

Taken together, Rogers highlighted the importance of the gut microbiome in the treatment of cancer patients with chemotherapy.  

Expert Commentary:

Question: What about antibody therapies in cancer, do these have the same impact on gut microbiota?

Answer: I don’t have the data, but I would guess that these effects we see are not limited to chemotherapy, and could also extend to other therapies.