Bacteria-Derived Sugar Promotes Intestinal Stem Cell Recovery

Researchers at the University of Toronto have made a significant discovery regarding how gut bacteria contribute to the regeneration of intestinal stem cells after injury. This revelation highlights an unexpected role of the gut microbiome in human health.

Traditionally, it was believed that gut microbes did not influence the functionality of intestinal stem cells during normal conditions. However, in a recent study, Ph.D. candidate Shawn Goyal and his advisor, Stephen Girardin, a professor specializing in immunology and laboratory medicine, explored the potential of the microbiome to support stem cell function during periods of intestinal damage and repair. Their findings, published in Cell Stem Cell, carry implications for conditions such as colorectal cancer and inflammatory bowel disease.

Stem cells are known for their remarkable capacity to replicate themselves and differentiate into various cell types. During embryonic development, these cells transform into the diverse cell types that constitute the body's organs and tissues. This regenerative capability persists into adulthood, with stem cells located throughout the body, including the intestines, where they are responsible for regenerating the intestinal lining every few days.

The intestinal stem cell layer serves as a crucial barrier, safeguarding the underlying tissues from partially digested food, microbes, toxins, and other harmful substances. Under healthy conditions, this layer remains sterile, but exposure to microbial byproducts can signal that potentially harmful agents have penetrated this barrier.

According to Girardin, bacteria can infiltrate areas that should remain sterile, necessitating a defense mechanism to protect the stem cells essential for maintaining the intestinal barrier. In their study, the researchers utilized mouse and cell models to identify a specific sugar produced by bacteria, known as ADP-heptose, which activates a signaling pathway leading to the destruction of intestinal stem cells.

This stem cell loss directly affects intestinal development. When exposed to ADP-heptose, lab-grown intestinal organoids--miniature 3D tissue models--exhibited reduced size and lacked the intricate architecture typical of healthy tissues. Furthermore, ADP-heptose initiated a regenerative program in stem cells, prompting Paneth cells, a particular type of intestinal cell, to revert to a stem cell state. These so-called revival stem cells played a crucial role in replenishing the lost stem cells and restoring the integrity of the intestinal barrier.

The researchers propose that this protective mechanism proactively eliminates stem cells that may be damaged by toxins or microbes and replaces them with healthy cells to help restore the intestinal lining. Girardin points out that bacterial exposure can lead to DNA damage, which, when accumulated, may result in cancer, inflammatory bowel disease, and other health issues. He is keen to investigate this link further in upcoming research.

"Could we have discovered a mechanism by which stem cells exposed to microbes are replaced, thereby reducing the risk of mutations that could lead to colorectal cancer?" he inquires. His lab is also examining whether antiviral defenses have a similar role in maintaining the intestinal lining.

Girardin credits the germ-free facility at the Temerty Medicine's division of comparative medicine for enabling his research group to explore the role of gut microbes effectively. Despite the challenges and costs associated with maintaining germ-free facilities, he acknowledges their necessity for conducting these types of studies.

For further information, see Shawn Goyal et al, "Bacterial ADP-heptose triggers stem cell regeneration in the intestinal epithelium following injury," published in Cell Stem Cell (2025). DOI: 10.1016/j.stem.2025.06.009.