Diagnosis of Crohn's disease and ulcerative colitis using the microbiome

Abstract

Background: Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disease resulting from dysregulation of the mucosal immune response and gut microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are difficult to distinguish, and differential diagnosis is essential for establishing a long-term treatment plan for patients. Furthermore, the abundance of mucosal bacteria is associated with the severity of the disease. This study aimed to differentiate and diagnose these two diseases using the microbiome and identify specific biomarkers associated with disease activity.

Results: Differences in the abundance and composition of the microbiome between IBD patients and healthy controls (HC) were observed. Compared to HC, the diversity of the gut microbiome in patients with IBD decreased; the diversity of the gut microbiome in patients with CD was significantly lower. Sixty-eight microbiota members (28 for CD and 40 for UC) associated with these diseases were identified. Additionally, as the disease progressed through different stages, the diversity of the bacteria decreased. The abundances of Alistipes shahii and Pseudodesulfovibrio aespoeensis were negatively correlated with the severity of CD, whereas the abundance of Polynucleobacter wianus was positively correlated. The severity of UC was negatively correlated with the abundance of A. shahii, Porphyromonas asaccharolytica and Akkermansia muciniphilla, while it was positively correlated with the abundance of Pantoea candidatus pantoea carbekii. A regularized logistic regression model was used for the differential diagnosis of the two diseases. The area under the curve (AUC) was used to examine the performance of the model. The model discriminated UC and CD at an AUC of 0.873 (train set), 0.778 (test set), and 0.633 (validation set) and an area under the precision-recall curve (PRAUC) of 0.888 (train set), 0.806 (test set), and 0.474 (validation set).

Conclusions: Based on fecal whole-metagenome shotgun (WMS) sequencing, CD and UC were diagnosed using a machine-learning predictive model. Microbiome biomarkers associated with disease activity (UC and CD) are also proposed.

Keywords: Crohn’s disease; Gut microbiome; Inflammatory bowel disease; Machine learning; Ulcerative colitis; Whole metagenome shotgun (WMS) sequencing.