Fecal profiling of pancreatic cancer

Silvia Radrezza

05.01.2026

Results of a recent study showed reduced microbial diversity and distinct microbial profile in the two groups of PC patients.

What is already known

Pancreatic cancer (PC) is a significant challenge in oncology due to its late-stage diagnosis and limited treatment options. Current screening methods are insufficient, pointing the research into stool-based assays and microbial classifiers as potential early detection markers.

What this research adds

This study compared the stool microbiota of PC patients (33 Finnish and 50 Iranian) and healthy controls (35 Finnish and 34 Iranian) using 16S rRNA gene sequencing. The populations were choosen based on the geographical and cultural differences.

Conclusions

Results showed reduced microbial diversity and distinct microbial profile in the two groups of PC patients. Overall, a higher abundance of facultative pathogens and lower abundance of beneficial bacteria were observed. A microbial classifier for predicting PC was confirmed in both cohorts. A comprehensive understanding of the role of the gut microbiome in PC could significantly enhance early detection efforts and improve patient outcomes.

A study, recently published in Gut Pathogens, aimed to compare the gut microbiota of pancreatic ductal adenocarcinoma (PDAC) of two very different populations, Finnish and Iranian (n=33 and n=50 respectively) with related healthy controls (n=35, n=34).

Despite a significant decrease in cancer mortality, PC remains a therapeutic challenge for incidence and mortality. Indeed, early detection screenings are not available at the moment. On the other hand, differentially expressed gut microbes have been proposed as stool biomarkers. The results so far are, however, sparce and controversial. The aim of this study was to expand the current understanding of PC gut microbiota taking into account the population differences and to contribute to the development of an early screening method. Here the major findings.

Alpha diversity in PC gut microbiota

• Finnish and Iranian PDAC patients showed significantly lower alpha diversity than healthy controls. Indeed, Shannon entropy, Chao 1 index, and phylogenetic diversity were significantly reduced in PDAC patients.
• No significant impact of age, alcohol consumption, biliary stenting, neoadjuvant treatment, sex, or smoking on microbial diversity were found in the Finnish cohort. However, obese Finns had significantly lower species richness than normal weight individuals of the same group.
• Smoking and age significantly impacted alpha diversity in the Iranian cohort.
• Shannon entropy and Chao 1 index were significantly lower in smokers than nonsmokers.

Microbial community composition in PC patients and healthy controls

• 16,343 OTUs were identified and assigned to 15 phyla, 26 classes, 110 families, and 348 genera.
• The Finnish PDAC gut microbiota showed the following composition: 41% Firmicutes, 40% Bacteroidota, 8% Proteobacteria, 5% Verrucomicrobiota, 3% Actinobacteriota, 1% Fusobacteriota. There was a difference for the healthy Finnish with 50% Firmicutes, 34% Bacteroidota, 5% Proteobacteria, 4% Verrucomicrobiota, and Fusobacteriota, but higher Actinobacteriota.
• Iranian PDAC gut microbiota showed: 48% Firmicutes, 25% Bacteroidota, 15% Proteobacteria, 6% Actinobacteriota, 5% Verrucomicrobiota.
• Top ten genera in Finnish PDAC patients were: Bacteroides, Alistipes, Faecalibacterium, Akkermansia, Parabacteroides, Bifidobacterium, Escherichia-Shigella, Roseburia, Ruminococcus, and Subdoligranulum.
• Patients and controls within and between cohorts showed significant differences in microbial community composition.
• There were no significant differences between treated and untreated patients or those with and without biliary stents in the Finnish cohort.
• There were significant differences in the Iranian cohort between age groups, sexes, and smoking habits.

PC gut microbiota in the Finnish and Iranian cohorts

After a general comparison, the researchers compared the microbiota composition at phylum, family and genus level.

Phylum-level Differences

• PDAC patients in both Finnish and Iranian cohorts showed greater abundances of Fusobacteriota and Synergistota.
• Iranian PDAC patients had higher abundances of Verrucomicrobiota and Proteobacteria and a lower abundance of Elusimicrobiota while Finnish patients had a greater abundance of Campylobacterota than their respective healthy controls.

Family-level Differences

• 26 families differed between patients and controls in the Finnish cohort, 23 in the Iranian cohort.
• Families with higher abundance in PDAC patients included Entererococcaceae, Fusobacteriaceae, and Enterobacteriaceae.
• In detail, Finnish PDAC patients presented with higher abundances of Yersiniaceae, Hafniaceae, and Campylobacteraceae while Iranian PDAC patients showed higher levels of Lactobacillaceae, Akkermansiaceae, and Streptococcaceae compared with their respective healthy controls.

Genus-level Differences

• 78 taxa differentially abundant between patients and controls were detected in the Finnish, 67 in the Iranian cohort
• The most abundant genera in PDAC in both populations included Enterococcus, Sellimonas, Veillonella, Klebsiella, Hungatella, Eisenbergiella, Fusobacterium, Enterobacter, Flavonifractor, and Coprobacillus.
• Genera with lower abundance common to both populations were Asteroleplasma, Clostridia UCG-014, and Butyricicoccaceae UCG-009.

Overall, the two populations showed several differences. In particular:
• Iranian patients presented significantly greater abundances of Thermoplasmatota, Synergistota, Proteobacteria, Actinobacteriota, and Firmicutes then Finnish PDACs
• Finnish PDAC patients showed significant enrichment of the phyla Campylobacteriota, Cyanobacteria, and Bacteroidota.
• In terms of biomarkers, both populations of PDAC samples were enriched in Klebsiella and Hungatella and depleted of Agathobacter, Anaerostipes, and Clostridia. Finnish PDAC samples were enriched in Christensenellales, Rhodospirillales, Enterobacter, Enterococcus, Citrobacter, Campylobacter, and Oscillospira and depleted in Prevotella_9, Butyrivibrio, Butyricicoccus, Lachnospira, and Romboutsia. Iranian PDAC samples instead showed higher presence of Subdoligranulum, Streptococcus, Lactobacillus, Limosilactobacillus, Klauyvera, and Pantotea with a depletion of Faecalibacterium, Bifidobacterium, Dialister, Blautia, Roseburia, Parasutterella, and Ruminococcus.

Functions of PC gut microbes and pathway analysis

Applying KEGG term analysis, 6417 functions remained after filtering.

• Significant differences were observed between the Finnish and the Iranian PC patients in microbial functions.
• Only 40 of the 500 most distinctive predicted microbial functions overlapped between populations.
• Top four differing predicted functions in PDAC patients versus healthy controls – i.e. Clumping factor B, accessory secretory protein Asp3, and ATP-binding cassette subfamily C.
• The Finnish cohort showed high depletion of predicted functions including rsbT antagonist protein RsbS, serine/threonine-protein kinase RsbT, and rsbT coantagonist protein RsbR; membrane-bound hydrogenase subunit alpha in Iranian patients.
• Pathway analysis revealed enriched peptidoglycan biosynthesis, galactose metabolism, lysine biosynthesis, and furfural degradation pathways.

Statistical analyses and machine learning models were then applied to validate the predictions showing great results (AUC of 0.85 at phylum level).

To conclude, “We observed consistent trends in PC-related microbial diversity and community composition in our two populations—Finnish and Iranian—with profoundly different environments and lifestyles.” This suggests how the gut microbiota plays a crucial role in the development of PC, with increased pathogenic microbes and depletion of protective ones. This unique microbial profile could be used for noninvasive early PC screening, but further research is needed to explore integrating probiotics with conventional drugs.