Cancer patients suffer from drug side effects. This is because chemotherapy drugs attack not only cancer cells but also normal cells. American researchers have found an important clue about the toxicity of chemotherapy drugs in the gut microbiome. If the toxicity of chemotherapy drugs can be adjusted to match the patient, a way to increase the effectiveness of cancer treatment without side effects can be found.
A research team led by Professor Peter Turnbaugh of the University of California, San Francisco (UCSF) School of Medicine announced on the 17th that they revealed the relationship between the side effects of the widely used chemotherapy drug "fluoropyrimidine" and gut bacteria in gastrointestinal cancer treatment. The research findings were published in the international journal "Science Translational Medicine" on the same day.
Chemotherapy drugs are highly effective at killing cancer cells, but they also come with significant side effects, including cardiac toxicity, gastrointestinal disorders, numbness in the hands and feet, and weight loss. In particular, fluoropyrimidine has significant side effects for some patients, with 1 in 10 needing to stop treatment.
The research team collected credit entries from 40 colorectal cancer patients before and after chemotherapy to observe changes in gut bacteria and analyzed this in relation to chemotherapy side effects. As a result, it was found that the balance of gut microorganisms was disrupted after chemotherapy administration, with some bacteria decreasing, but the bacteria with the "preTA" gene increased.
The preTA gene breaks down the toxic component of chemotherapy drugs, "5-fluorouracil (5-FU)," into less harmful substances. This means that the more bacteria with preTA there are, the fewer side effects from chemotherapy may occur. To confirm that this trend is not limited to patients in specific regions, the research team additionally analyzed data collected from 33 colorectal cancer patients in the Netherlands. The analysis showed that, similar to U.S. patients, the diversity of gut microorganisms decreased after fluoropyrimidine treatment, and a pattern of increasing bacteria with the preTA gene was observed.
The research team conducted experiments on mice to more directly verify the role of preTA. Mice that had their gut bacteria eliminated with antibiotics experienced more severe side effects from chemotherapy, but when E. coli carrying the preTA gene was reintroduced, weight loss and intestinal damage significantly decreased.
The same trend was confirmed in humans. Patients with a high number of gut bacteria possessing the preTA gene experienced fewer side effects from chemotherapy, and the balance of gut microorganisms was also better maintained.
Based on the research findings, the team also developed an algorithm to predict the risk of chemotherapy side effects by measuring the amount of the preTA gene. In the future, it is expected that treatments managing side effects can be implemented by testing the amount of the preTA gene in gut bacteria before chemotherapy or by preemptively introducing beneficial bacteria that carry the preTA gene.
Kai Trepka, a doctoral researcher at UCSF, noted, "This discovery shows that gut microorganisms are a key factor in determining drug response, beyond merely serving a digestive assist role," and added, "In the future, personalized chemotherapy that considers an individual's gut microbiome status will be much closer to reality."
References
Science Translational Medicine (2025), DOI: https://doi.org/10.1126/scitranslmed.adq8870