New study from the GIMM Foundation shows that the evolution of E. coli bacteria, which is present in most human intestines, is conditioned by the immune system.

In a human intestine, there are as many bacteria as human cells in the entire body. Among these bacteria, there is one called Escherichia coli, or E. coli, which can colonize the intestine in perfect harmony, but can also contribute to inflammatory bowel diseases or cause lethal diarrhea episodes, especially in children. As in any species, not all E. coli bacteria are the same. A healthy person can have more than one type of E. coli, and bacteria evolve over time, with an innocuous E. coli potentially becoming a pathogenic agent. But what influences the evolution of an E. coli that colonizes an organism? In an article published today in the scientific journal PLOS Pathogens*, the team led by Isabel Gordo, principal investigator at the GIMM Foundation – Gulbenkian Institute for Molecular Medicine, explored the role of the immune system in the evolution of these bacteria. This work can have important implications for understanding what leads a bacterium to evolve towards causing disease.

Interested for many years in how bacteria and the immune system interact, Isabel Gordo questioned whether E. coli evolution is affected by the immune system of the organism where it is found. The research team then followed the evolution of two different strains of the bacteria in the intestines of mice with normal and compromised immune systems. “We discovered that the two E. coli strains co-exist with different abundances in the intestine for thousands of bacterial generations, and that the evolution of each strain is affected by the mouse’s immune system,” says Isabel Gordo, the study’s leader.

When we talk about human evolution, we’re talking about a process that takes thousands of years. In bacteria, evolution is much faster. In one hour, an E. coli can divide in a mouse’s intestine, giving rise to a new generation. With each division, random changes in DNA can occur that can have various consequences: they can lead to the bacterium’s death, they may not cause any change in how the bacterium survives, or they can make that bacterium better adapted to its environment and divide more.

Of all the DNA changes that may arise, the study’s greatest discovery focused on those that increase the bacterium’s resistance in the intestine. “Specific mutations that lead to better E. coli adaptation were observed only in mice with a capable immune system,” says Camille Ameline, the study’s first author. It’s as if the pressure of a healthy immune system on bacteria forces them to try to survive, promoting these DNA mutations.

Regarding the importance of discovering the immune system’s influence on bacterial evolution, Elsa Seixas, also a first author of the study, adds that “this bacterium, E. coli, is present in most humans, and for this reason, it is crucial to understand how the evolution of bacteria in our intestine is shaped by the immune system.”

*Ameline C, Seixas E, Barreto HC, Frazão N, Rodrigues MV, Ventura MR, Lourenço M, Gordo I (2025) Evolution of Escherichia coli strains under competent or compromised adaptive immunity. PLOS Pathogens. DOI: 10.1371/journal.ppat.1012442