Pancreas
Gut. 2022;71(7):1359–72
A fecal microbiota signature with high specificity for pancreatic cancer
Background: Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) etiology and progression.
Objective: To explore the fecal and salivary microbiota as potential diagnostic biomarkers.
Methods: The authors 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: Fecal 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 the microbiome-based predictions were combined 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 fecal PDAC marker species were detectable in pancreatic tumor and non-tumor tissue using 16S rRNA sequencing and fluorescence in situ hybridization.
Conclusion: Taken together, these results indicate that non-invasive, robust and specific fecal microbiota-based screening for the early detection of in pancreatic ductal adenocarcinoma is feasible.