A study suggests that certain bacteria in the colon produce a new class of genotoxic molecules that promote the development of colorectal cancer.
Two-thirds of all cases of colorectal cancer occur in people with no family history or who do not have inherited genetic mutations that predispose to this cancer. In the vast majority of cases, external factors, often related to lifestyle, are responsible for the accumulation of mutations in DNA that are essential for the onset and progression of colorectal cancer.
Bacteria under the magnifying glass
In addition to well-documented risk factors for colorectal cancer such as excess weight, physical inactivity, and diet (too much meat, not enough vegetables), more and more researchers are interested in the contribution of gut bacteria, the microbiome, to the development of this disease. cancer.
For example, it has been shown that some bacteria (Fusobacterium nucleus) are present in large numbers in colorectal tumors and play a crucial role in their development 1.
It appears that the gut microbiome has another, more dangerous way of causing colorectal cancer by producing DNA-damaging toxins to create genetic mutations.
One of the best examples of this is colibactin, which is produced by certain strains ofEscherichia coli Which fuses the two DNA strands together and causes breaks that can promote genomic instability necessary for tumor progression 2.
Novel toxins for the genome
A recent study suggests that this type of carcinogenic toxin would also be responsible for the increased risk of colorectal cancer observed in patients with inflammatory bowel disease such as ulcerative colitis or Crohn’s disease.
By analyzing the major bacteria found in the stool of 11 patients with one or more of these diseases, researchers identified 18 strains capable of DNA damage, including bacteria named Morganella Morganiwhich is known to be present in higher amounts in the microbiomes of patients with inflammatory bowel disease as well as those with colorectal cancer.
Further biochemical analysis enabled them to show that the genotoxins produced by these bacteria were hitherto unknown molecules, which they called indoleamines.
In a mouse model of colorectal cancer, intestinal colonization by strains Morgani Significantly increases the number of tumors that develop in response to a carcinogen.
It seems that indoleamines are responsible for accelerating tumor progression, because the elimination of the gene responsible for the synthesis of these genotoxins by these bacteria eliminates this carcinogenic effect.
Until now, it was thought that the increased risk of colorectal cancer in people with IBD was mainly a result of the chronic inflammation caused by these diseases. The results of this study suggest that imbalances in the microbiome, along with toxic molecules produced by microbial metabolism, could also play a major role in the development of this cancer.
Because the indoleamines identified in this study are all composed of three essential amino acids (leucine, valine and phenylalanine), it will be interesting to determine whether changes in dietary protein intake to reduce these amino acids can influence colorectal cancer risk.
1. Rubinstein MR et al. Fusobacterium nuclei promote colorectal carcinogenesis by modulating E-cadherin/b-catenin signaling via FadA adhesin. host cell microbe 2013; 14: 195-206.
2. Nougayrède JP et al. coli induces DNA double-strand breaks in eukaryotic cells. Science 2006; 313:848-51.
3. Cao Y et al. Shared microbiota from patients with IBD produce genotoxic metabolites. Sciencepublished October 28, 2022.
