Fecal Microbiome Promising for Early Pancreatic Cancer Detection

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is usually diagnosed in an advanced stage, when treatment options are limited and the prognosis is poor. To date, carbohydrate antigen CA 19-9 is the only established biomarker in PDAC but it has limited specificity, and is therefore mostly used for PDAC surveillance rather than for screening or diagnosis. Thus, there is an urgent need to identify novel non-invasive markers for early detection of PDAC. There is increasing evidence that microbiota are associated with carcinogenesis, including in PDAC. Ongoing trials are exploring how the microbiome may be used for the early diagnosis, prevention, and treatment of cancer.

In a recently published case-control study conducted in Spain, the authors sought to identify microbial predictive signatures of pancreatic cancer using oral and intestinal microbiota. The study included 57 patients with newly diagnosed PDAC, 29 patients with chronic pancreatitis and 50 matched control (patients who were hospitalized with other diseases not related to PDAC risk factors). The investigators collected saliva and stool samples, as well as normal and tumor pancreatic tissue from participating patients, and extensive patient metadata, including clinical and demographic data. They assessed microbial composition in each sample by using whole-genome shotgun metagenomics and 16S rRNA amplicon sequencing. They found that only patients’ fecal microbial composition, not saliva or any metadata variable, was significantly associated with PDAC. Using biostatistical and bioinformatic analyses, the investigators developed gene signature based on 27 fecal microbial species, which identified PDAC with an accuracy of 0.84 area under the receiver operating characteristic curve (AUROC). Accuracy was consistent across early and advanced stages of pancreatic cancer. The predictive power was further improved to up to 0.94 AUROC when investigators combined microbiome-based predictions with serum levels of CA 19-9. The prediction accuracy of microbiome signature was further validated in an independent German study and in 5792 publicly available gut metagenomes from 25 studies across 18 countries and 9 disease types. 

In addition, a comparison of the fecal microbiome signature in patients with PDAC with that of the pancreatic microbiome was performed and showed that many of the bacteria characteristic of pancreatic cancer fecal samples were also present in tumor tissue, with Lactobacillus sp., Akkermansia muciniphila and Bacteroides sp. enriched in tumor tissue but not in normal tissue. The implications of the presence of these bacteria for pancreatic cancer progression remain to be investigated.

In their conclusion, the investigators highlighted that using patients’ fecal microbiome for the detection of PDAC is feasible and represents a “non-invasive, cost-effective and robust approach to early PDAC diagnosis.” The authors of an accompanying commentary noted that this study clarified the ‘’connection between fecal microbiome signature and PDAC and represents significant progress for non-invasive cancer detection’’. Although the results are promising, they suggest further evaluation in prospective cohorts to estimate clinical impact.

Kartal E et al. Gut. 2022 Mar 8. [Online ahead of print].