Researchers at Uppsala University have utilized lab-grown miniature intestines to uncover the mechanisms through which aggressive Shigella bacteria infect the human gut. This breakthrough study paves the way for using cultured human mini-organs to explore various severe infections.

Understanding how human-specific bacteria cause illness is a complex task, as traditional laboratory animals do not always accurately represent human physiology. In a recent publication in Nature Genetics, researchers have demonstrated the feasibility of utilizing cultured mini-organs to map the colonization of human intestinal mucosa by bacteria. The focus of the study was on Shigella, a bacterium that leads to severe intestinal inflammation in humans and is responsible for a significant number of deaths each year, particularly in young children.

Lead author Maria Letizia Di Martino stated, 'For the first time, we have managed to identify the genes required by Shigella to induce infection using a human model that mimics intestinal tissue. This study also highlights the potential of using cultured human mini-organs to study various serious infections, especially those for which the lack of suitable laboratory animal models has been a hindrance.'

Intestinal Models Derived from Stem Cells

Shigella bacteria are invasive pathogens that utilize various mechanisms to invade the body's tissues and manipulate immune system functions. In this study, researchers concentrated on identifying the genes responsible for producing these mechanisms. They created intestinal organoids - miniature intestinal models developed from human stem cells obtained from surgical waste material. By employing a method that randomly disrupts bacterial genes, the team assessed how these alterations impacted Shigella's ability to infect the human intestinal model. This approach allowed the researchers to create the initial comprehensive map of the genes utilized by Shigella to invade human intestinal tissue. Additionally, the tactics employed by this bacterium to attack tissue shed light on how other dangerous bacteria, which possess similar mechanisms, can infect organs like the lungs and urinary tract.

Professor Mikael Sellin, another lead author of the study, remarked, 'Although Shigella has approximately 5,000 genes, we discovered that only around 100 are essential for the bacterium to colonize tissue and cause severe infection. This list of genes is invaluable for comprehending the progression of infections and developing novel treatments that can disrupt the pathogenic behavior of the bacteria.'

The research was a collaborative effort involving Uppsala University, Uppsala University Hospital, the Helmholtz Institute for RNA-based Infection Research (HIRI) in Germany, Toronto University in Canada, and Umeå University.