Integrating gut microbiota and metabolites to decode variations in magnetic resonance enterography features of bowel damage in Crohn's disease: development of a multi-scale diagnostic model
Lili Huang, Guangzhou / China
Author Block: L. Huang, R. Zhang, X. Shen, Y. Wang, X. Wang, Z. Li, Z. Li, X. Li; Guangzhou/CNPurpose: Bowel damage (BD) significantly impacts Crohn's disease (CD) patient's prognosis, showing varied magnetic resonance enterography (MRE) features. This study seeks to investigate the potential mechanisms underlying MRE features of BD using multi-scale data and develop an optimal diagnostic model for BD.Methods or Background: 230 CD patients were prospectively recruited and categorized into BD (n=103) and non-BD (n=127) using the Lémann index. All patients underwent MRE. Faecal 16S rRNA gene sequencing, and faecal and blood metabolomics were conducted. Relationships between MRE findings, gut microbiota, and faecal/blood metabolites were analysed using causal mediation analysis. Diagnostic models for BD were constructed using gut microbiota, faecal metabolites, blood metabolites, and MRE findings alone or in combination, with their performance assessed using ROC analysis.Results or Findings: Seven MRE features, including penetration, bowel thickness, and perienteric T2WI signal, differed significantly between BD and non-BD patients. The components of gut microbiota and faecal/blood metabolites were distinct between the two groups. Causal mediation analysis revealed that Blautia may promote intestinal penetration accompanied by perienteric inflammation (i.e., perienteric T2WI signal) through faecal arachidonic acid and blood ceramide (d18:2/23:1). Individual component models, including intestinal microbiota, faecal metabolites, and blood metabolites, yielded AUCs of - 588 (95% CI: 0.453 - 0.713), 0.671 (95% CI: 0.538 - 0.787), 0.640 (95% CI: 0.533 - 0.737), respectively. Incorporating MRE into these factors to construct a multi-scale model increased the AUC by 0.708 (95% CI: 0.582 - 0.823).
Conclusion: BD-induced MRE findings are partially attributable to microbial and metabolite factors, providing novel insights into the possible mechanisms driving these MRE alterations. The inclusion of MRE enhances diagnostic performance of the multi-scale model for BD, rendering it a promising tool for BD diagnosis.Limitations: The diagnostic model lacks validation in an external dataset.Funding for this study: No funding was received for this study.Has your study been approved by an ethics committee? YesEthics committee - additional information: This study was approved by the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University (No. IIT-2021[215], Guangzhou, China).