Gut bacteria like Escherichia Coli are essential for human health, but a toxin they produce, called colibactin, may help cancer resist therapies. Credit: Olga Reukova/ Getty Images. 
The microbiota has many important functions, but scientists know that some bacteria can also trigger the development of cancer. In particular, some species of Escherichia Coli in the gut can produce colibactin, and in some colorectal tumours the presence of this toxin increases. “This toxin can cause the transformation of normal intestinal cells into tumours by inducing mutations, that is, alterations in the sequence of their DNA, which is also the target of chemotherapeutics commonly used in the clinic,” explains Bardelli. The team wondered whether the exposure to the toxin could influence the way in which tumours respond to treatments.
To simulate what happens in the intestine, the scientists grew colorectal cancer cells and colibactin-producing bacteria and used organoids, that are three-dimensional cultures derived from patients. The team has collected thousands of samples through the years2. By exploiting sequencing and bioinformatic analysis, they noted that colibactin trains tumour cells to withstand a constant load of DNA mutations. When the tumour is treated with irinotecan, a widely used chemotherapy drug that has a similar mechanism of colibactin, the tumour is already trained. “Having learned to tolerate the mutations caused by colibactin, the tumour becomes resistant to the damage caused by chemotherapy,” explains Bardelli.
The discovery might have important translational implications, helping clinicians select the best chemotherapy drug for each tumour. “Our goal is now to validate this preclinical approach on larger and more representative cohorts of colon cancer patients,” says Bardelli.
