RT Journal Article SR Electronic T1 A faecal microbiota signature with high specificity for pancreatic cancer JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1359 OP 1372 DO 10.1136/gutjnl-2021-324755 VO 71 IS 7 A1 Ece Kartal A1 Thomas S B Schmidt A1 Esther Molina-Montes A1 Sandra Rodríguez-Perales A1 Jakob Wirbel A1 Oleksandr M Maistrenko A1 Wasiu A Akanni A1 Bilal Alashkar Alhamwe A1 Renato J Alves A1 Alfredo Carrato A1 Hans-Peter Erasmus A1 Lidia Estudillo A1 Fabian Finkelmeier A1 Anthony Fullam A1 Anna M Glazek A1 Paulina Gómez-Rubio A1 Rajna Hercog A1 Ferris Jung A1 Stefanie Kandels A1 Stephan Kersting A1 Melanie Langheinrich A1 Mirari Márquez A1 Xavier Molero A1 Askarbek Orakov A1 Thea Van Rossum A1 Raul Torres-Ruiz A1 Anja Telzerow A1 Konrad Zych A1 MAGIC Study investigators A1 PanGenEU Study investigators A1 Vladimir Benes A1 Georg Zeller A1 Jonel Trebicka A1 Francisco X Real A1 Nuria Malats A1 Peer Bork YR 2022 UL http://gut.bmj.com/content/71/7/1359.abstract AB Background Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) aetiology and progression.Objective To explore the faecal and salivary microbiota as potential diagnostic biomarkers.Methods We applied shotgun metagenomic and 16S rRNA amplicon sequencing to samples from a Spanish case–control study (n=136), including 57 cases, 50 controls, and 29 patients with chronic pancreatitis in the discovery phase, and from a German case–control study (n=76), in the validation phase.Results Faecal metagenomic classifiers performed much better than saliva-based classifiers and identified patients with PDAC with an accuracy of up to 0.84 area under the receiver operating characteristic curve (AUROC) based on a set of 27 microbial species, with consistent accuracy across early and late disease stages. Performance further improved to up to 0.94 AUROC when we combined our microbiome-based predictions with serum levels of carbohydrate antigen (CA) 19–9, the only current non-invasive, Food and Drug Administration approved, low specificity PDAC diagnostic biomarker. Furthermore, a microbiota-based classification model confined to PDAC-enriched species was highly disease-specific when validated against 25 publicly available metagenomic study populations for various health conditions (n=5792). Both microbiome-based models had a high prediction accuracy on a German validation population (n=76). Several faecal PDAC marker species were detectable in pancreatic tumour and non-tumour tissue using 16S rRNA sequencing and fluorescence in situ hybridisation.Conclusion Taken together, our results indicate that non-invasive, robust and specific faecal microbiota-based screening for the early detection of PDAC is feasible.Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information. The raw sequencing data for the samples are made available in the European Nucleotide Archive (ENA) under the study identifiers PRJEB38625 and PRJEB42013. Metadata for these samples are available as Supplementary Tables S1 and S2. Filtered taxonomic and functional profiles used as input for the statistical modelling pipeline are available in Supplementary Data S1 and S2. Analysis code and results available under https://github.com/psecekartal/PDAC.git.