02 April 2021

Crohn's disease and Escherichia

Geneticists have accused E. coli proteins of complicity in Crohn's disease

Scientists hope that thanks to their discovery it will be possible to create a cure for this disease

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Proteins produced by one of the strains of E. coli are one of the key factors in the appearance of Crohn's disease – a severe inflammatory bowel disease. This conclusion was reached by Canadian biologists, whose article was published by the scientific journal Nature Communications (Elhenawy et al., High-throughput fitness screening and transcriptomics identify a role for a type IV secret system in the pathogenesis of Crohn's disease-associated Escherichia coli).

"The intestinal surface of 70-80% of patients with Crohn's disease is populated with E. coli, which belongs to the AIEC strain. Until recently, we did not know how they are related to this disease, nor what role they play in its development. Now we assume that these microbes are the cause of its occurrence," said Brian Coombs, one of the authors of the study, professor at McMaster University (Canada).

Crohn's disease is one of the relatively severe chronic inflammatory bowel diseases. As a rule, patients with it have multiple foci of inflammation, ulcers and scars on the walls of the intestine, esophagus and other parts of the gastrointestinal tract. They do not disappear without medical intervention.

Scientists do not know the causes of this disease. Presumably, both genetic factors and bacterial infections or parasitic worms are involved in this, which disrupt the normal functioning of the immune system of the digestive system and cause it to attack the cells of the esophagus and intestines.

In a new paper, Coombs and his colleagues have found out the possible cause of Crohn's disease. They studied bacteria that live on the surface of damaged intestinal walls and are present in large quantities in other regions of the digestive system of carriers of this disease.

The attention of biologists was attracted by one of the strains of E. coli, AIEC, which was recorded in almost all patients. It actively multiplied both on the surface and inside the damaged tissues of the digestive system, and also displaced all other competing types of bacteria.

Interested in the ability of this strain to penetrate the intestinal walls, biologists have studied in detail the structure of its DNA. Having isolated a set of several hundred genome regions active only in the AIEC strain, the scientists tried to figure out their role in the life of microbes by randomly disabling them.

Experiments on mice showed that disabling one of these sets of genes, T4SS, prevented inflammation and other consequences of Crohn's disease. This was due to the fact that the loss of this part of the genome deprived E. coli of the ability to form protein biofilms on the intestinal surface.

Scientists suggest that the appearance of this biofilm leads to the development of chronic inflammation and contributes to the formation of a comfortable habitat for AIEC. Interestingly, genes from the T4SS family were turned on in E. coli only when microbes got into the intestines of rodents, which once again indicates their direct connection with Crohn's disease.

Coombs believes that the results of their work pave the way for the creation of drugs for this disease that will be able to fight its cause, not the symptoms.

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