Two recent studies from the University of California, Riverside (UCR), published in Gut Microbes, highlight the role of the PTPN2 gene in protecting the gut from harmful bacteria associated with inflammatory bowel disease (IBD).
Led by Declan McCole, a professor of biomedical sciences at UCR, the research indicates that improper PTPN2 function increases the gut's susceptibility to infection and inflammation.
Individuals with IBD often exhibit elevated levels of AIEC, a type of E. coli bacteria that can attach to, invade, and damage the gut lining, exacerbating inflammation.
Normally, PTPN2 supports gut health by regulating inflammation and maintaining a balanced gut microbiome. However, some IBD patients possess a mutated version of this gene, resulting in reduced PTPN2 activity. This impairment disrupts gut bacterial balance, making the gut more vulnerable to harmful microbes. McCole and his team observed that this diminished protection allows bacteria like AIEC to attach to and invade intestinal cells more readily.
"These findings help explain why certain individuals are more susceptible to persistent gut inflammation," McCole stated. "The research also suggests potential treatment strategies to restore gut defenses and limit harmful bacteria in patients with a genetic predisposition to IBD."
The first study, titled 'The PTPN2 rs1893217 IBD risk allele increases susceptibility to AIEC invasion by a JAK-STAT-CEACAM6 axis,' examined gut tissue from IBD patients with the faulty PTPN2 gene and engineered lab-grown gut cells. It revealed that non-functional PTPN2 leads to an increase in cellular 'docking sites,' facilitating AIEC entry into cells. Treatment with JAK inhibitors, a medication used for IBD, was found to partially mitigate this issue by reducing bacterial invasion.
The second study, 'Intestinal epithelial PTPN2 limits pathobiont colonization by immune-directed antimicrobial responses,' reported that PTPN2 assists gut lining cells in combating bacteria like AIEC by producing natural antimicrobial substances and fortifying the gut barrier. This protective mechanism is effective against both normal and harmful bacteria, preventing adverse microbes from entering gut cells and initiating inflammation.
Both papers were published in the December 2025 issue of Gut Microbes. The National Institutes of Health provided support for this research.