Using patient saliva and stool samples, researchers found that it may be possible to spot the malignancy through a specific panel of microbes, regardless of the stage of disease, they report in Gut.
"Pancreatic cancer is linked to a specific gut microbial signature that may be used for disease screening in the future and hopefully enable earlier detection and improve prognoses for patients," said study coauthor Thomas Sebastian Schmidt, a research scientist at EMBL Heidelberg, in Germany.
"Ours is an early work," Schmidt told Reuters Health by email. "The way to a screening test to be used in the clinic is still far off. However we took some care to vet our microbiome models towards disease specificity. To be useful in practice, a screening test should be sensitive, but more importantly specific. Test specificity in particular has been an issue with previous efforts, and also for microbiome signatures in other diseases where very few associations have proven to generalize beyond initial studies."
To explore the possibility that pancreatic cancer might produce a specific microbiome signature, Schmidt and his colleagues conducted a case-control study with subjects prospectively recruited between 2016 and 2019 from the Hospital Ramon y Cajal in Madrid and the Hospital Vall d'Hebron in Barcelona, Spain.
The discovery phase of the study included 57 newly diagnosed patients older than 18 who had not yet received treatment, 29 patients with chronic pancreatitis, a known risk factor for PDAC and 50 controls matched for age, gender and hospital who did not have any PDAC risk factors.
The researchers obtained 100 spit and 212 stool samples from the study subjects, along with pancreatic tissue from the 57 newly diagnosed patients, 25 of whom had early stage disease and 32, advanced disease.
Using a machine learning model and accounting for known risk factors, such as smoking, drinking, obesity and diabetes, the researchers discovered a distinct microbial profile in the stool samples of people with PDCA compared to both those with chronic pancreatitis and those in the control group.
The technique identified a characteristic enrichment of certain microbe species and a relative scarcity of others. Methanobrevibacter smithii, Fusobacterium nucleatum, Alloscardovia omnicolens, Veillonella atypica and Bacteroides finegoldii were abundant in the stool samples of the cancer patients while Faecalibacterium prausnitzii, Bacteroides coprocola, Bifidobacterium bifidum or Romboutsia timonensis were depleted.
Schmidt and his colleagues validated the predictive ability of the microbial profile in a separate group of 76 Germans, 44 of whom had PDAC and 32 of whom did not. They next validated the profile against publically available data from 25 studies which included 5,792 samples from patients with nine different health conditions, including other cancers and type-2 diabetes. That exercise revealed a weakness of the model - a 15% false-positive rate that was associated mostly with Crohn's disease and liver cirrhosis.
In the future, "if microbiome-based PDAC screening does become available, it will be one tool among many for early detection of this disease," Schmidt said. "In fact, we found that our models were complementary to the only existing (US Food and Drug Administration)-approved PDAC biomarker - blood serum levels of carbohydrate antigen 19-9 which is unfortunately not PDAC-specific - and a combination of both was far more accurate predictor than either microbiome or serum marker individually. This, too, makes us optimistic about the future translation of our findings to the clinic."
The new study doesn't shed light on the question of whether the microbes in the signature might lead to the development of pancreatic cancer or just be a response to changes in the patient related to the disease, said Dr. Jonathan Jacobs, an assistant professor in the Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, and director of the UCLA Microbiome Core.
But, he said, "Even without knowing if the microbes are driving the disease, you have the potential for a very sensitive biomarker to screen or solidify a diagnosis."
"There is a need for early detection of pancreatic cancer since it typically doesn't show up until it's inoperable. A non-invasive marker would be very useful. There is nothing currently available," Dr. Jacobs, who was not involved in the new research, told Reuters Health by phone.
"This study was based on a modest sample size," he said. "But they validated it with two independent cohorts and that made it much more powerful than if they had only used their own cohort."
Schmidt and several of his co-authors have a pending patent application for early detection of pancreatic cancer based on microbial biomarkers.
SOURCE: https://bit.ly/3tJvNcx and https://bit.ly/3MGpVJG Gut, online March 8, 2022.
By Linda Carroll
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