Noninvasive microbiota-based diagnostic models for pancreatic ductal adenocarcinoma: a systematic review and diagnostic test accuracy meta-analysis

Background Due to delays in diagnosis, many patients with pancreatic ductal adenocarcinoma (PDAC) miss the window for curative interventions. The oral and gut microbiomes are attractive as noninvasive triage instruments; however, while the literature provides AUROC values, it has not established clinically useful thresholds. Objective To systematically assess the diagnostic performance and clinical maturity of noninvasive microbiota-derived tools for identifying PDAC. Methods Following PRISMA 2020 and PRISMA-DTA, we searched eight databases up to April 19, 2026, and conducted a targeted supplementary search on September 3, 2026. Risk of bias was assessed using PROBAST and QUADAS-2. The nine-row meta-analysis, which included approximations and correlated estimates, was exploratory. Results The initial search and targeted supplementary search yielded 16 studies covering 21 sample-domain items; 20 model-based records constituted the units of analysis for the risk-of-bias assessment. Fifty-one AUROC estimates formed a separate list of discrimination estimates. Six-row fixed-threshold data from five studies constituted the primary descriptive core. Sensitivity ranged from 0.682 to 0.964, and specificity ranged from 0.667 to 0.963. The exploratory nine-row bivariate model yielded pooled sensitivity of 0.86 (95% CI 0.80–0.90) and specificity of 0.80 (95% CI 0.73–0.86). These nine rows represented seven studies; Li 2025 and Chen 2025b each provided a correlated row, so the pooled estimates were hypothesis-generating. The certainty of evidence was rated very low using an adapted, GRADE-informed appraisal. All model-based rows (20/20) were at high risk of bias in the PROBAST analysis domain and high overall risk on QUADAS-2. Although stool-based testing provided the clearest signal of external validation, benign pancreatic mimics remained underrepresented. Conclusion Detecting PDAC via noninvasive microbiota classifiers carries a biologically plausible yet very low-certainty diagnostic signal. Current findings do not support stand-alone clinical deployment and support only exploratory adjunctive triage. Validating prospectively against benign pancreatic mimics is mandatory before routine clinical adoption. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261370926 , Identifier, CRD420261370926.