Non-Invasive Analysis of Gut Microbiome Biomarkers Enhances Diagnosis of IBD

More Patients, Difficult Diagnostics

Idiopathic inflammatory bowel diseases, most commonly represented by Crohn's disease and ulcerative colitis, are chronic recurring inflammatory diseases of the digestive tract, and their incidence is continually rising due to current lifestyles. It is estimated that more than 7 million people worldwide are currently living with IBD. Advanced progression of the disease is often associated with the need for drastic surgical intervention in the form of intestinal resection.

A key factor for the best prognosis and effective treatment is early diagnosis, which currently is not easy. It typically consists of several separate examinations from clinical history, laboratory blood and stool tests, colonoscopy with histological examination to other imaging methods of the digestive tract. No universal test for direct diagnosis of IBD currently exists.

This could be changed by the findings of a study by scientists from the University of Hong Kong, who focused on developing a non-invasive and more reliable diagnostic method. Recent studies have suggested that idiopathic inflammatory bowel diseases may be accompanied by changes in the composition of the gut microbiota.

For example, in more than half of the patients with Crohn's disease, there is an increased occurrence of adherent invasive Escherichia coli or toxigenic Bacteroides fragilis. In patients with ulcerative colitis, an increased occurrence of Gemella morbillorum is noticeable. In both cases, however, there is a noticeable decrease in species diversity among bacteria with anti-inflammatory properties. Until now, however, it was unclear how to utilize these gut microbiome biomarkers in the diagnosis of IBD.

Detailed Analysis of the Microbiome Aids in Constructing a Diagnostic Panel

Initially, the research team focused on a detailed analysis of the gut microbiome of patients with IBD. In doing so, they analyzed data from 4,406 samples across 13 research cohorts from eight world regions – Hong Kong, mainland China, Australia, the United States, the Netherlands, Spain, Denmark, and the United Kingdom.

They compared the composition of the gut microbiota in healthy controls and patients with ulcerative colitis and Crohn's disease. They managed to identify a total of 1,175 animal taxa – 3 kingdoms, 14 phyla, 25 classes, 40 orders, 85 families, 226 genera, and 788 species. Generally, they found significantly reduced microbial diversity and bacterial quantities in patients with IBD compared to healthy individuals.

In all detected profiles of the gut microbiome in individual research cohorts, the scientists looked for patterns that showed certain characteristics of correlation. Based on this, they selected ten bacterial species as biomarkers for ulcerative colitis and nine bacterial species as biomarkers for Crohn's disease. From these, they constructed the first version of a diagnostic model and compared it with various stages and manifestations of both diseases. This enabled them to assemble a universal panel of biomarkers that can reliably distinguish patients with IBD from healthy individuals.

Developing a Suitable Diagnostic Tool for Practical Use

The biomarker panel itself is not yet sufficient for common use. To utilize it as a diagnostic method in clinical practice, it needs to be transformed into a simple and cost-effective diagnostic tool. Therefore, at the end of their study, the researchers also focused on developing a diagnostic method based on multiplex digital droplet polymerase chain reaction (m-ddPCR) for quantifying individual species in stool samples. Further development of the biomarker panel will depend on the results of additional studies.

In conclusion, the researchers admit that their study exhibited some limiting factors. These could include, for example, potential, albeit unlikely, bias in selecting individual cohorts and the yet undetermined influence of certain external factors, such as diet and medication. Nonetheless, the conclusions of their research should serve as a solid foundation for further detailed studies that will complete the development of the diagnostic test for regular clinical practice.

Editorial Team, Medscope.pro

Source: Zheng, J., Sun, Q., Zhang, M. et al. Noninvasive, microbiome-based diagnosis of inflammatory bowel disease. Nat Med 2024, doi: 10.1038/s41591-024-03280-4. [Epub ahead of print]