Lab-Grown Intestines Reveal Shigella's Genetic Arsenal

Using lab-grown miniature intestines, researchers at Uppsala University have mapped how aggressive Shigella bacteria infect the human gut. This breakthrough paves the way for exploring a variety of other serious infections through the use of cultured human mini-organs (1^✔ ✔Trusted Source
A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen

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A New Era with Human Mini-Guts

Understanding how human-specific bacteria make us sick is challenging, as laboratory animals rarely reflect human physiology. In a new study published in Nature Genetics, researchers show that it is now possible to use cultured mini-organs to map how bacteria colonize the human intestinal mucosa.

The team focused specifically on Shigella, a bacterium that causes severe intestinal inflammation in humans and is responsible for over 200,000 deaths per year, particularly among young children.

“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,” says researcher Maria Letizia Di Martino, one of the study’s lead authors.

Shigella bacteria are invasive pathogens that attack the body’s tissues using a variety of ‘weapons’ to invade into the intestinal mucosa and manipulate the body’s immune system functions. In the current study, the researchers focused on identifying the genes responsible for producing these weapons.

To do this, they generated intestinal organoids – miniature intestinal models grown from human stem cells purified from surgical waste material.

They then used a method that randomly knocks out bacterial genes and tested how these changes affected Shigella’s ability to infect the human intestinal model. This approach enabled the team to generate the first comprehensive map of the genes Shigella uses to invade human intestinal tissue.

The strategy this bacterium uses to attack tissue also informs on how other dangerous bacteria – that share similar weaponry – can infect the lung and urinary tract, for example.

“This list is a goldmine for understanding the progression of infections and for developing new treatments that can ‘turn off’ the bacteria’s pathogenic behaviour,” says Professor Mikael Sellin, another of the study’s lead authors.

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

Reference:

1. A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen - (https://www.nature.com/articles/s41588-025-02218-x)

Source-Eurekalert