A study published in Cell Stem Cell revealed a surprising mechanism by which the gut microbiome influences human health with potential implications for colorectal cancer and inflammatory bowel disease.

While earlier research suggested gut microbes don’t affect intestinal stem cells under normal conditions, PhD student Shawn Goyal and his supervisor Stephen Girardin, a professor of immunology and laboratory medicine at U of T’s Temerty Faculty of Medicine explored whether the microbiome supports stem cell function during intestinal injury and repair.

Using mouse models and lab-grown cell systems, the team discovered that a unique bacterial sugar, ADP-heptose, activated a signaling pathway that led intestinal stem cells to self-destruct. This stem cell loss impaired intestinal development. When intestinal organoids miniature 3D tissue models were exposed to ADP-heptose they were smaller and lacked the complex structure seen in healthy tissues.

The researchers discovered that ADP-heptose also triggered a regenerative stem cell program prompting Paneth cells a specialized type of intestinal cell to revert to a stem cell state. These revival stem cells were vital for replacing lost stem cells and restoring the integrity of the intestinal barrier. This finding raises an intriguing question: why would a bacterial sugar induce both the destruction and renewal of intestinal stem cells? Stem cells are remarkable for their ability to self-renew and differentiate into multiple cell types and while embryonic stem cells form all tissues during early development stem cells continue to play a critical role throughout life in maintaining and repairing tissues.

Our bodies constantly need to regenerate tissues due to daily wear and tear and ongoing insults says Goyal. In adults stem cells are present throughout the body including the intestine where they renew the intestinal lining every few days. This lining acts as a crucial barrier protecting underlying tissues from microbes toxins and other harmful substances while allowing nutrients to pass through. Intestinal stem cells and Paneth cells are normally located in a sterile region of the intestine and when exposed to microbial byproducts it signals a breach in this barrier indicating that potentially harmful microbes or substances have entered.

Bacteria can invade areas where they shouldn’t, so it’s crucial to activate a defense program to protect stem cells, which are essential for maintaining the intestinal barrier,” says Girardin. The researchers propose that this protective pathway eliminates intestinal stem cells that may be damaged by toxins or microbes and replaces them with healthy ones to restore the lining. Girardin notes that bacterial exposure can cause DNA damage which over time may contribute to cancer inflammatory bowel disease, and other conditions and he plans to investigate this further. Could this mechanism by replacing stem cells exposed to microbes serve as a protective strategy against colorectal cancer? he asks. His lab is also examining whether antiviral defenses might similarly help preserve the intestinal lining.

Source: https://temertymedicine.utoronto.ca/news/study-reveals-how-bacterial-signal-triggers-intestinal-stem-cell-regeneration