Antibiotic overuse, a driver of antimicrobial resistance, is a global public health problem. In 2010, estimated global antibiotic consumption was at least 10 doses per person. Multiple studies indicate that antibiotic use, even with narrow-spectrum antibiotics, changes the gut microbiota.
Along with our colleagues from Johns Hopkins University School of Medicine and University of East Anglia Norwich (UK), we sought to investigate the long-term health outcomes from oral antibiotic use, focusing on colorectal cancer (CRC). For a study published in Gut, we conducted a matched case control study in the United Kingdom Clinical Practice Research Datalink (CPRD). A total of 166,057 participants were analyzed. With a median follow up of 8 years, 70% of participants received oral antibiotics, with most prescribed more than one type during the study period.
After controlling for potential confounding factors (factors that increase CRC risk such as weight, smoking, and alcohol intake), we found colon cancer risk increased with even one antibiotic course, with maximal increased risk (15%) after 30 days of antibiotic exposure. This association of antibiotic exposure and increased colon cancer risk was observed only in the proximal colon. Antibiotics that kill anaerobic bacteria— in particular penicillins—appeared to drive the risk. Further, increased risk for colon cancer after antibiotic exposure was linked to antibiotic use more than 10 years before the cancer diagnosis, suggesting a long-term impact of antibiotics on the gut microbiota and also consistent with the usual slow growth of colon tumors.
With our colleagues, we observed that antibiotic exposure, particularly to tetracyclines, was associated with decreased rectal cancer risk, but only after 60 days of exposure. The differences observed in the associations between antibiotic exposure and colon versus rectal cancer are consistent with the differing biology of these two cancer types.
Our findings support, but do not prove, the potential causal link between disrupted microbiota and CRC. More clinical and translational studies are needed to confirm and extend this work to determine how the colonic microbiota contributes to CRC disease. Regardless, this study highlights the importance of judicious antibiotic use by physicians, even beyond concerns for antimicrobial resistance and Clostridioides difficile infection.
