An international research group led by Victoria Pascal from the Department of Gastroenterology, Vall d'Hebron Research Institute in Barcelona, has succeeded in identifying patients with Crohn's disease (CD) solely from stool samples.
With a sensitivity of 80% and a specificity of 89 to 94%, scientists were able to distinguish Crohn patients from healthy control patients, patients with ulcerative colitis (UC), irritable bowel syndrome (IBS) and anorexia nervosa (AN). The following proved to be diagnostically effective in:
The authors assume that their non-invasive method can enable the diagnosis of Crohn's disease if no specific characteristics of the disease can or have been detected in its early phase. Due to the equally high reliability of stool samples from four European countries, the researchers assume that their method is independent of geographical characteristics of the intestinal flora.
The starting point of the study was the search for a clear dysbiosis assignment to chronic inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC). The scientists first analyzed stool samples from 178 subjects from Spain (including healthy, unrelated control subjects [HC]: 40, patients with CD: 34; patients with UC: 33; healthy related control subjects [HR]: 36 for CD patients, 35 for UC patients). Subsequently, the study was repeated on a comparable population in Belgium and subsequently extended to a total of 2,045 participants from Spain, Belgium, Great Britain and Germany (HC: 1247, CD: 339, UC: 158, IBS: 202, AN: 99).
To distinguish the microbial genera present in the samples, the researchers used 16S rRNA sequencing of ribosomal RNA. The statistical analysis of the 115 million amino acid sequences obtained was used by the UniFrac metric to express the differences between the encountered intestinal flora in the form of a biological distance (see Fig. 1C) (see Source 2).
The evaluation of the stool samples showed the following results (see Fig. 1):
Fig. 1: Microbial markers to distinguish CD and UC (A) in the discovery study (n = 178), (B) in the verification study (n = 2,045). Blue strokes indicate proof of the corresponding genus, whereby lighter shades indicate lower and darker shades indicate greater colonization. Patient groups are marked by colour: blue: HC and HR; red: CD; yellow: UC; green: IBS; violet: AN. (C) UniFrac Principal Coordinate Analysis with the coordinates PC1, PC2, PC3 between two patient groups. In all four partial illustrations, patients with Crohn's disease (CD) proved to be significantly different from the respective comparison group (p < 0.001) (Sources: 1)
1. Pascal V et al. A microbial signature for Crohn's disease. Good 2017;66:813-822.
2nd Lozupone C, Knight R. UniFrac: A New Phylogenetic Method for Comparing Microbial Communities. Applied and Environmental Microbiology 2005:71(12):8228-8235.