DNA Levels in Stool Samples Could Provide Non-invasive Test to Track Disease and Treatment Efficacy

May 14, 2026 – A new test using DNA from human stool samples could become a simple noninvasive tool for tracking disease activity in inflammatory bowel disease (IBD), a disease affecting an estimated 6–8 million people worldwide.

According to a new study published in Microbiome, researchers at the Hebrew University of Jerusalem (HU) demonstrated that human DNA in stool, previously ignored as biological noise, provides a clear map of activity in IBD. The researchers found that immune cells called neutrophils, which migrate to the gut in response to inflammation, are a biomarker in stool that closely reflects disease severity in both children and adults.

Today, many patients with Crohn’s disease and ulcerative colitis must undergo repeated colonoscopies to monitor inflammation. This new approach suggests that a simple stool test could help track flare-ups and treatment response over time, reducing reliance on invasive procedures.

The team found that neutrophil levels in stool accurately reflect the severity of gut inflammation in both children and adults, by analyzing the origin of this DNA through methylation profiling. This dual approach of monitoring both host and microbiome data offers a non-invasive way to track disease flares and treatment efficacy over time.

“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, of the HU Rachel and Selim Benin School of Computer Sciences and Engineering. “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.”

The researchers found that levels of neutrophil DNA strongly correlate with established clinical markers, such as fecal calprotectin, reinforcing its value as a reliable indicator of disease activity. Furthermore, calprotectin assays have their own detection limits, hindering their efficacy in most severe cases.

Key Findings

New Biomarker: Neutrophil DNA levels accurately reflect disease severity and flare-ups in IBD patients.

Improved Metric: A newly developed measure, the Neutrophil-to-Epithelial Ratio (NER), more effectively distinguishes between remission and active disease.

Predictive Power: Combining human DNA signals with microbiome data, machine learning models were able to predict IBD and differentiate between Crohn’s disease and ulcerative colitis.

This dual analysis of human and microbial DNA opens the door to a new generation of noninvasive diagnostic tools. By capturing both the body’s immune response and the composition of the microbiome, clinicians may be able to monitor disease progression more accurately and adjust treatments earlier.

The researchers hope this approach will lead to routine stool-based monitoring, improving care and quality of life for millions of people living with IBD.

The study was supported by the Helmsley Charitable Trust and conducted in collaboration with the Faculty of Medicine at HU and the Pediatric Gastroenterology Institute at the Shaare Zedek Medical Center.