Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia

Adenomas and carcinomas of the intestine are often colonized by bacteria. Australian researchers have examined whether this can be used for early detection or even treatment of colorectal cancer. They published their findings in the journal Nature Communications (2024; DOI: 10 1038 / s41467-024-44776-4).

Although the Escherichia coli strain Nissle 1917 (EcN) is used as a probiotic to improve intestinal flora, the chances of the bacteria surviving in the intestines are low. After treatment, they are detected in stool only for a few weeks.

It’s a different story with adenomas and tumors. They often colonize EcN for a longer period. The team led by Susan Woods from the Adelaide Medical School recently demonstrated this in a clinical study of 35 patients with colorectal cancer.

Patients were treated with a commercial EcN preparation or placebo for 14 days before surgery on the large intestine: then bacteria were found in higher concentrations only in the carcinoma after surgery, but were not detected in the surrounding area.

This selective uptake of EcN was also found in mice. The researchers then equipped the bacteria with the genome of an enzyme that produces salicylates. Salicylates enter the blood through the tumor, and then are excreted by the kidneys.

In fact, in mice with colorectal cancer, the concentration of salicylate in urine increased up to 5 times after oral administration of genetically modified EcN. Woods believes that probiotics may be used for early detection of colorectal cancer. However, whether they can do this remains to be shown in clinical trials.

The researchers also consider therapeutic possibilities. In one experiment, they linked EcN with nanotubes that neutralize PD-L1 and CTLA-4 antigens. These are two important “immune checkpoints” that cancer cells use to protect themselves from attack by the immune system. The researchers used it to turn probiotics into a delivery system for checkpoint inhibitors.

In one experiment, mice with mutations in the APC gene were treated. They develop familial adenomatous polyposis (FAP), as do humans with the same mutation. Since carcinomas can form in adenomas, the treatment of FAP involves total colectomy.

A 47% reduction in adenomas was observed in mice after treatment with EcN. Similarly, whether treatment with modified probiotics can save FAP patients from colectomy will only be determined in a clinical trial.