Journal of Crohn's & colitis · 2026
Inflammatory bowel disease (IBD) is associated with increased intestinal extrachromosomal circular DNA: an emerging biomarker for IBD type and activity.
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Petito Valentina, Gerovska Daniela, Piazzesi Antonia, di Vincenzo Federica, Russo Alessandra, Turchini Laura, Masi Letizia, Emoli Valeria, Tabolacci Elisabetta, Giustiniani Maria Cristina, Mazza Tommaso, Laterza Lucrezia, Papa Alfredo, Lopetuso Loris R, Putignani Lorenza, Gasbarrini Antonio, Araúzo-Bravo Marcos J, Scaldaferri Franco
Аннотация
BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a gastrointestinal, auto-inflammatory disease with a chronic relapsing and remitting course, whose diagnosis is based on several examinations assessing intestinal inflammation and clinical assessment. Furthermore, only 40%-60% of patients respond to therapy, making identification of reliable markers of disease or predictors of disease course and therapy response of great interest to the medical community. The existence of extrachromosomal circular DNA (eccDNA) is well established, and has become a promising biomarker for different types of cancer. Here, we investigate eccDNA in patients affected by IBD.
METHODS: Intestinal biopsies were collected from patients and from healthy controls. Circular DNA was enriched, sequenced, identified with Circle Finder, and annotated with bedtools. Patients were then stratified based on disease type and activity.
RESULTS: Intestinal tissue from IBD patients contained significantly higher levels of eccDNAs than tissue from healthy controls. eccDNA production also was significantly increased in patients with active ulcerative colitis compared to patients in remission. In Crohn's disease, eccDNAs were more abundant than in healthy controls, though the difference between active and inactive Crohn's disease was less defined. Furthermore, eccDNAs containing fragments from specific genes were consistently found in a large proportion of patients with IBD, while healthy controls presented with a more stochastic eccDNA pattern.
CONCLUSIONS: Here, we uncover an IBD-specific pattern of eccDNA production from intestinal biopsies. Furthermore, we have identified genic hotspots that characterize active disease. We propose that eccDNA containing specific gene fragments (eg, NRG1 and ZPMF2) could represent a promising new biomarker tool for patients with IBD.
METHODS: Intestinal biopsies were collected from patients and from healthy controls. Circular DNA was enriched, sequenced, identified with Circle Finder, and annotated with bedtools. Patients were then stratified based on disease type and activity.
RESULTS: Intestinal tissue from IBD patients contained significantly higher levels of eccDNAs than tissue from healthy controls. eccDNA production also was significantly increased in patients with active ulcerative colitis compared to patients in remission. In Crohn's disease, eccDNAs were more abundant than in healthy controls, though the difference between active and inactive Crohn's disease was less defined. Furthermore, eccDNAs containing fragments from specific genes were consistently found in a large proportion of patients with IBD, while healthy controls presented with a more stochastic eccDNA pattern.
CONCLUSIONS: Here, we uncover an IBD-specific pattern of eccDNA production from intestinal biopsies. Furthermore, we have identified genic hotspots that characterize active disease. We propose that eccDNA containing specific gene fragments (eg, NRG1 and ZPMF2) could represent a promising new biomarker tool for patients with IBD.