Researchers at Uppsala University have successfully used lab-grown miniature intestines to study how Shigella bacteria infect the human gut. This breakthrough paves the way for investigating various serious infections using cultured human mini-organs.

Understanding how bacteria specific to humans cause illnesses is a complex task, especially since laboratory animals do not always reflect human physiology.

A recent study published in Nature Genetics showcases the ability to utilize cultured mini-organs to map how bacteria colonize the human intestinal mucosa. The focus of the research was on Shigella, a bacterium that leads to severe intestinal inflammation and causes over 200,000 deaths annually, mainly among young children.

Lead author Maria Letizia Di Martino states, "For the first time, we have been able to map the genes Shigella needs to cause infection using a human model that mimics intestinal tissue. The study also demonstrates that cultured human mini-organs can now be used to investigate a variety of serious infections, particularly those for which the lack of laboratory animal models has previously limited research."

Intestinal models derived from stem cells

Shigella bacteria are invasive pathogens that utilize various mechanisms to invade the body's tissues and manipulate the immune system. The research team focused on identifying the genes responsible for these mechanisms.

To achieve this, they created intestinal organoids - miniature intestinal models grown from human stem cells obtained from surgical waste material. By randomly knocking out bacterial genes and observing how these changes impacted Shigella's ability to infect the human intestinal model, the team generated a comprehensive map of the genes used by Shigella to invade human intestinal tissue.

Professor Mikael Sellin, another lead author of the study, explains, "Shigella has around 5,000 genes, but we found that only about 100 of them are necessary for the bacterium to colonize tissue and cause aggressive infection. This list is a valuable resource for understanding the progression of infections and developing new treatments that can disrupt the bacteria's pathogenic behavior."

The collaboration involved in the study includes Uppsala University, Uppsala University Hospital, the Helmholtz Institute for RNA-based Infection Research (HIRI) in Germany, Toronto University in Canada, and Umeå University.