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Faecal Microbiota Signatures: Detecting Pancreatic Cancer Early with High Specificity

Written by Sharmin Begum, Science Writer 

Researchers have identified faecal microbiome signatures that may enable the early detection and screening of pancreatic ductal carcinoma (PDAC).  

In a study published by the British Medical Journal (BMJ), researchers in Germany explored the potential for early and accurate detection of PDAC using diagnostic biomarkers found in faecal and salivary microbiota. They analysed faecal and saliva based metagenomic classifiers for microbial species in a statistical model. Samples were sequenced from a Spanish cohort and then validated with a German cohort. Disease specificity was further validated against existing datasets from different diseases. 

“The high lethality of PDAC is a consequence of both late diagnosis and limited therapeutic options. At present, PDAC is diagnosed using imaging tests. Sensitive and affordable tests for an early detection of PDAC could therefore improve outcome”, says Ece Kartal, first author on the report in the BMJ. 

Clinical diagnostic need 

Whilst the incidence of pancreatic cancer remains relatively low, prognosis is poor due to the lack of robust diagnostic and screening tools to detect the disease early. Ece Kartal and colleagues have been investigating methods to improve the landscape of pancreatic cancer diagnosis. Pancreatic cancer cases are rising, with pancreatic ducal carcinoma (PDAC) being the most common form of the disease. In most cases, diagnosis is made in the late-stages of the disease when patients become symptomatic and present with non-resectable metastatic tumours. In the UK, only around 25% of pancreatic cancer patients survive at least a year after their diagnosis. 

PDAC is currently diagnosed with imaging tests. Whilst they prove valuable, they are limited in their ability to provide an accurate differential diagnosis between PDAC and chronic pancreatitis, as well as accurate disease staging. The only FDA  approved diagnostic biomarker currently available is blood serum levels of carbohydrate antigen (CA) 19-9, secreted by pancreatic tumours. However, this biomarker has limited specificity, as it can be raised in other health conditions.  This poses the need for more accurate diagnostic tests to screen and detect the disease earlier . 

Microbiome association with PDAC 

Ece Kartal and his team at Embl in Germany have been investigating previous research that indicates an increased risk of pancreatic cancer being linked with changes in oral, faecal and pancreatic microbiome composition.  

Researchers investigated potential diagnostic biomarkers in faecal and salivary microbiota in newly diagnosed PDAC patients prior to treatment, and in patients with chronic pancreatitis . Genetic sequencing was performed on 136 samples from a Spanish population in the discovery phase and 76 samples from a German population in the validation phase.  

Disease-specific associations were found in nine species. Species including Veillonella atypical, Fusobacterium nucleatum/hwasookii and Alloscardovia omnicolens were significantly enriched in faecal samples of PDAC patients. Species found to be depleted in PDAC patient faecal samples included Bacteroides coprocola, Romboustsia timonensis, Faecalibacterum prausnitzii and Bifidobacterium bifidum. There were no species associations detected from the salivary microbiota that were indicative of PDAC, as opposed to previous reports.  

After assessing 27 species in a statistical model, results demonstrated that the faecal metagenomic classifiers performed better at detecting PDAC than salivary classifiers in patients, regardless of which stage the disease was at. The accuracy of microbiome predictions improved when combined with blood serum CA tests from 0.84 to 0.94. Species enriched in PDAC patients were found to be highly disease-specific when analysed against an existing metagenomic study population of nine different health conditions in a sample size of 5792. Possible associations to oral and intestinal populations in several PDAC enriched species also indicates their role in disease progression. 

Researchers established that faecal microbiome models could accurately predict pancreatic PDAC in the Spanish cohort, which was further validated in the German cohort.  Some microbial populations in faecal samples, detected by fluorescence in-situ hybridisation (FISH) and RNA sequencing, were also found in both healthy and tumour pancreatic tissues. The study determined that using faecal microbiota is accurate, non-invasive and robust, and it may therefore be possible to screen and detect the early stages of pancreatic cancer. 

Clinical impact 

The findings from this study potentially change the landscape forthe prognosis of pancreatic cancer patients. The study gives hope for improved survival rates of future pancreatic cancer patients, with earlier, more accurate and less-invasive diagnosis on the horizon. With further research in faecal microbiota signatures, the potential for an approved PDAC screening test with a better understanding of the cause and treatment of the disease looks encouraging. “We believe that the presented panel of PDAC associated bacterial species may be relevant beyond their use for diagnosis, providing promising future entry points for disease prevention and therapeutic intervention” says Kartal.

Image Credit: Canva