The noninvasive detection of pancreatic ductal adenocarcinoma (PDAC) remains an immense challenge. Inthis study, we proposed a robust, accurate, and noninvasive classifier, namely Multi-Omics Co-training Graph Convolutional Networks (MOCO-GCN). It achieved high accuracy (0.9 0.06), F1 score (0.9 0.07), and AUROC (0.89 0.08), surpassing contemporary approaches. The performance of model was validated on an external cohort of German PDAC patients. Additionally, we discovered that the exposome may impact PDAC development through its complex interplay with gut microbiome by mediation analysis. For example, Fusobacterium hwasookii nucleatum, known for its ability to induce inflammatory responses, may serve as a mediator for the impact of rheumatoid arthritis on PDAC. Overall, our study sheds light on how exposome and microbiome in concert could contribute to PDAC development, and enable PDAC diagnosis with high fidelity and interpretability.