Stool DNA Analysis Tracks Disease Activity in IBD

Inflammatory bowel disease (IBD) affects an estimated 6–8 million people worldwide and is commonly monitored through colonoscopy and stool testing. Because disease activity can fluctuate, laboratories need noninvasive markers that reflect intestinal inflammation in real time. Human DNA in feces has traditionally been treated as background rather than a measurable analyte. New findings show that cell-of-origin analysis of fecal human DNA can help index disease activity in both pediatric and adult IBD.

Researchers at the Hebrew University of Jerusalem, with Shaare Zedek Medical Center, outline a stool-based approach that profiles human DNA fragments using methylation to determine their cellular origin. The analysis shows that DNA derived from neutrophils dominates the human signal in stool from patients with IBD, rather than colon epithelial DNA as previously assumed. By explicitly measuring host DNA alongside microbial features, the method provides a composite view of gut inflammation.

Image: Using a method that identifies the origin of DNA fragments, researchers found neutrophil levels closely reflected gut inflammation severity in pediatric and adult patients (photo credit: Shutterstock)

The study, published in Microbiome, examined pediatric patients in Israel and adult patients in the Netherlands, demonstrating consistent results across ages. Neutrophil DNA levels in stool correlated with established clinical markers, including fecal calprotectin. The authors also introduce a Neutrophil-to-Epithelial Ratio (NER), which more effectively distinguishes remission from active disease than assessing either component alone.

In addition to correlation with current markers, combining human DNA signals with microbiome data enabled machine learning models to predict IBD and differentiate Crohn’s disease from ulcerative colitis. The investigators note that calprotectin assays have detection limits that can hinder assessment in the most severe cases, whereas host DNA profiling captures real-time immune activity. Collectively, the findings suggest a path toward noninvasive, longitudinal monitoring of disease flares and treatment response using a simple stool sample.

“For too long, the human DNA found in stool samples was treated as biological ‘noise’ that we filtered out to focus on microbial data,” said Prof. Moran Yassour, from Hebrew University.

“Our findings show that this DNA contains valuable, unappreciated information, reflecting the immune system’s activity in real time. By analyzing both the human and microbial components together, we can gain a much clearer picture of what is happening in the gut.”

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