A breakthrough study published on Tuesday by Hebrew University shows that stem cells in the gut actively defend the body against dangerous infections like Salmonella.
The peer-reviewed study found that intestinal stem cells can actively respond to Salmonella infection and help protect the gut from bacterial invasion.
The research paper, titled “An inflammasome-driven differentiation program in intestinal stem cells protects against Salmonella infection,” which was led by PhD student Sacha Lebon and published in the Nature Immunology magazine, demonstrates that intestinal stem cells can directly sense intracellular Salmonella enterica bacteria and activate an inflammasome-dependent response.
This is a natural immune response that relies on the formation and activation of a multiprotein complex called an inflammasome to defend against pathogens or cellular stress.
Salmonella is a bacterial genus that causes a common foodborne intestinal illness, with gastrointestinal symptoms developing within 72 hours of exposure. Most Salmonella infections resolve in a few days without specific treatment, and this study from the Hebrew University shows why.
The study found that when a Salmonella infection is detected, stem cells in your gut rapidly differentiate into specialized cells known as antimicrobial Paneth cells.
Antimicrobial Paneth cells secrete molecules that help limit bacterial persistence, making it harder for illness-causing bacteria to survive in the gut.
Study mapped early responses to Salmonella
Dr. Matan Hofree, who supervised the study, explained: “Our findings show that intestinal stem cells are not only responsible for tissue regeneration, but also participate directly in the early defense against bacterial infection.”
Using single-cell RNA sequencing, lineage tracing, organoid models, and genetic perturbation approaches, the team mapped early responses to Salmonella infection at high resolution.
The study identified a rapid remodeling process in the intestinal epithelium driven by stem-cell differentiation toward antimicrobial cell types.
“Our results suggest that stem cell differentiation is part of an intrinsic protective program that helps preserve intestinal function during infection,” said Dr. Moshe Biton, the study’s supervisor from the Weizmann Institute.
The study also found a link between the Salmonella-associated stem cell signature and Crohn’s disease.
They saw that the stem cell signature was enriched in the intestinal stem cells of patients with Crohn’s disease - pointing to a possible connection between epithelial defense pathways, the first line of defense in the body’s immune response, and inflammatory bowel disease.
The work was carried out in collaboration among researchers at the Weizmann Institute of Science, the Hebrew University of Jerusalem, Sheba Medical Center, Hadassah–Hebrew University Medical Center, Tel Aviv University, and Cincinnati Children’s Hospital Medical Center.