A faecal microbiota signature with high specificity for pancreatic cancer

Kartal E, Schmidt TSB, Molina-Montes E, Rodriguez-Perales S, Wirbel J, Maistrenko OM, Akanni WA, Alashkar Alhamwe B, Alves RJ, Carrato A, Erasmus HP, Estudillo L, Finkelmeier F, Fullam A, Glazek AM, Gomez-Rubio P, Hercog R, Jung F, Kandels S, Kersting S, Langheinrich M, Marquez M, Molero X, Orakov A, Van Rossum T, Torres-Ruiz R, Telzerow A, Zych K, Benes V, Zeller G, Trebicka J, Real FX, Malats N, Bork P, Gut 71 (7) :1359-1372 (2022).


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.