New research has shown that one common bacteria strain Escherichia coli (E. coli) may be associated with the development of colorectal cancer (CRC).

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Scientists have warned that the use of certain probiotics that contain toxins secreting strains of E. coli, may adversely affect colorectal health in the long term.

The study was published in the magazine «Nature» on February 27. It was headed by scientists from the Institute Habrehta and the Center for Pediatric Oncology. Princess Maxima in Utrecht.

The scientists focused on a particular strain of E. coli that produces a toxin kolibaktin as the strain found in stool samples from people with colorectal cancer than in the stool samples of healthy people.

It is already known that kolibaktin causes DNA damage in cells in vitro, and investigators suspected that the toxin can do the same with the cells lining the intestines. To test this theory, they developed a small copy of the intestinal tissue, known as organelles human intestinal, and subjected to the cultured tissue to the toxins secreted by the strain of E. coli. They found that the bacteria induce a unique pattern of mutations in the DNA of human cells, whereas other strains of E. coli do not.

The command is then examined more than 5,500 tumor samples obtained from patients with CRC in the Netherlands and the United Kingdom. Scientists have discovered a unique pattern of mutation in about 5% of the tumors.

"Our study describes a distinct mutational signature in colorectal cancer and suggests that its underlying mutation process is directly related to the influence of the bacteria in the past," - commented the researchers.

They expressed the need for caution when using probiotic products, as some of them contain the same strain of E. coli, which was studied in the research.

"Currently on the market are probiotics that contain genotoxic strains of E. coli. Some of these probiotics are also used in clinical trials .... These strains should be re-tested in the laboratory. Although these probiotics can relieve some bodily discomfort in the short term, they can lead to cancer decades after the treatment "- warned the researchers.

The researchers have identified 18 genotoxic strains of Escherichia coli, which contain hybrid polyketide-peptide nonribosomalny operon synthase (pks) 50 kb responsible for production kolibaktina.

Kolibaktin and similar genotoxins damage human DNA in a specific mutation or signature. These signatures can play a big role in determining the causes of cancer and even direct treatment strategies.

Command investigated human intestinal organelles derived from primary crypt stem cells, performing injection cavity pks-positive strains of E. coli cells, as well as strains incapable of producing an active kolibaktin. After five cycles during the 5 months of bacterial injection, followed by culturing organelles within 2-3 weeks, scientists have estimated for the organelles of DNA damage. They identified pks-specific DNA base substitution of one other (SBS) and small signature indel (ID).

To determine whether the mutation found signs of human tumors, the researchers examined data from the sequencing of the entire genome of 3668 metastatic solid cancer.

The signature of SBS was observed in 7.5% of the tumors of colorectal cancer, and signature D - 8.8% of neoplasms, and both signatures together - 6.25% of colorectal tumors.

Scientists have discovered mutational signature in other types of cancer: 1.6% in head and neck tumors and 2% -4% of urinary tract tumors. They also studied the 2208 Genomes Project of colorectal cancer Genomics England 100,000 Genomes and found that these signatures were present in 4-5% of patients.

Source: https://www.medscape.com/viewarticle/926121

Date of publication: 
Wednesday, March 4, 2020