Professor of Cell and Developmental Biology Ken Lau and his lab published new research that challenges a longstanding assumption about Crohn’s disease: that all regions of the gut respond similarly to inflammation and treatment. The study, published in The Journal of Clinical Investigation and supported by multiple National Institute of Health grants, reveals that microbial interactions and genetic factors contribute to region-specific inflammation, particularly in the ascending colon—an often-overlooked site of disease.
“Our study addresses a critical and underexplored challenge in understanding and treating inflammatory diseases of the gut and shows that genetic and microbial interactions can drive inflammation in a region-specific manner,” said Lau. Lau is the director of the Vanderbilt Center for Computational Systems Biology.
Crohn’s disease, a type of inflammatory bowel disease, has traditionally been studied and treated as if the disease initiates and progresses through similar mechanisms regardless of where along the small intestine and colon it is located. However, the new findings suggest that inflammation in different regions of the intestine may arise through distinct mechanisms, requiring more targeted therapeutic approaches.
The study, which was led by graduate student Paige Spencer, focused on the role of Chlamydia muridarum, a bacterium that can trigger chronic inflammation in the ascending colon by upregulating the enzyme IDO1 in the gut’s epithelial cells. Using a combination of mouse models, microbial manipulations, human Crohn’s disease tissue samples, and advanced omics analyses, Lau’s lab uncovered several key findings:
- Chlamydia muridarum drives inflammation in a clinically relevant IBD model by upregulating IDO1 in gut epithelial cells.
- The ascending colon is particularly susceptible to this pathobiont-driven chronic inflammation. A pathobiont is a microbe that usually lives harmlessly in your body, but under certain conditions—like stress, illness, or changes in your environment—it can turn harmful and cause disease.
- Upregulation of epithelial IDO1 is conserved in Crohn’s disease specimens with active ascending colon inflammation, providing a potential therapeutic target.
These findings open the door for more personalized approaches to Crohn’s disease treatment. “We hope our findings motivate the development of region-specific treatment strategies and epithelia-targeted drugs,” Lau said. He added that, for his lab, “a long-term goal is to investigate IDO1 inhibitors, which could be repurposed for Crohn’s disease of the ascending colon.”
Lau emphasized that the study was a team effort, made possible through collaborations with researchers across Vanderbilt University Medical Center and beyond. “Having access to Vanderbilt’s core facilities—and the willingness of colleagues to share resources—accelerated our progress,” Lau said. “This work would not have been possible without our talented team of researchers, including undergraduate and graduate students, technicians, postdoctoral trainees, and clinician-scientists.”
The findings mark an important step toward developing more precise and effective treatments for Crohn’s disease, offering new hope for patients affected by this chronic condition.
Go deeper
The paper “Pathobiont-triggered induction of goblet cell response drives regional susceptibility to Inflammatory Bowel Disease was published in The Journal of Clinical Investigation in February 2026.
Funding
This work was supported by the National Institutes of Health, the Vanderbilt University Stanley Cohen Innovation Fund, an HHMI Gilliam Fellowship, the National Science Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, Crohn’s & Colitis Foundation, and the United States Department of Veterans Affairs.