Two recent studies from the University of California, Riverside, published in the same issue of Gut Microbes highlight the role of a gene called PTPN2 in protecting the gut from harmful bacteria linked to inflammatory bowel disease (IBD).

Led by Declan McCole, a professor of biomedical sciences in the School of Medicine, the studies show that when PTPN2 does not function properly, the gut becomes more vulnerable to infection and inflammation.

Declan McCole

People with IBD often have higher levels of AIEC, a harmful type of E. coli bacteria. AIEC can attach to the gut lining, invade gut cells, damage the gut’s protective barrier, and worsen inflammation.

Normally, PTPN2 helps maintain gut health by controlling inflammation and supporting a balanced gut microbiome. However, some people with IBD carry a faulty version of this gene, which reduces PTPN2 activity. When PTPN2 is impaired, the balance of gut bacteria is disrupted, making the gut more susceptible to harmful microbes.

McCole and his colleagues found that this loss of protection allows bacteria like AIEC to attach to gut cells, invade the intestinal lining, and multiply more easily.

“Our findings help explain why certain people are more prone to ongoing gut inflammation,” McCole said. “The research also points to potential treatment strategies that could restore gut defenses and limit harmful bacteria in patients who are genetically at risk for IBD.”

In the first paper, “The PTPN2 rs1893217 IBD risk allele increases susceptibility to AIEC invasion by a JAK-STAT-CEACAM6 axis,” the researchers examined gut tissue from IBD patients with the faulty PTPN2 gene, as well as lab-grown gut cells engineered with the same genetic change. They found that when PTPN2 is not functioning, gut cells produce more “docking sites” on their surface, allowing AIEC to enter the cells more easily.

“We also found that treatment with a medication already used to treat IBD, called a JAK inhibitor, could partially reduce this problem by limiting the bacteria’s ability to invade gut cells,” McCole said. “Our findings suggest that JAK inhibitors may help control harmful bacterial growth in people genetically predisposed to IBD.”

In the second paper, “Intestinal epithelial PTPN2 limits pathobiont colonization by immune-directed antimicrobial responses,” the researchers report that PTPN2 helps gut lining cells fight bacteria such as AIEC by producing natural bacteria-killing substances and maintaining a strong gut barrier.

“This protection works against normal gut bacteria as well as harmful bacteria, such as AIEC,” McCole said. “When PTPN2 functions properly, it helps prevent bad bacteria from entering gut cells and triggering inflammation.”

The two papers appear in the December 2025 Issue of Gut Microbes, a leading journal focused on host–microbe interactions.

The research was supported by grants from the National Institutes of Health.

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