Pancreatic cancer is one of the deadliest, with only around 13% of patients surviving five years after diagnosis; this disease is usually detected at advanced stages due to the lack of evident early symptoms, which is why identifying risk factors and early detection methods is crucial to improving prognosis. However, smoking, obesity, chronic pancreatitis, or certain genetic predispositions explain less than 30% of cases, leaving a large proportion of uncertain origin. In this context, a new study published in JAMA Oncology provides evidence that the oral microbiome could be a missing piece in the pancreatic cancer puzzle.

The oral microbiome is the set of microorganisms that live in our mouths, normally contributing to digestion and protecting oral health. For years, researchers suspected that oral health and pancreatic cancer could be related; in fact, several epidemiological studies have observed that people with periodontitis (a severe infection of the gums) or other indicators of poor oral health have a higher incidence of pancreatic cancer, as demonstrated by studies that have found antibodies in the blood against Porphyromonas gingivalis, a bacterium typical of periodontal disease, associated with higher risk of orodigestive cancer and even specifically of the pancreas. Taken together, these findings led to the hypothesis that certain oral microbes, both bacteria and fungi, could influence the development of pancreatic tumors.

To test this idea, a team of U.S. researchers analyzed saliva samples from more than 122,000 initially healthy individuals, followed for nearly a decade. During the follow-up, 445 participants developed pancreatic cancer and were compared with 445 similar individuals (of the same age, sex, race, etc.) who did not develop cancer during that period. The scientists extracted DNA from those oral samples and sequenced the microbial genetic material to profile each individual’s oral microbiome at an ultra-resolved level of detail. Subsequently, they employed advanced biostatistical methods to detect associations between the presence or abundance of each microbe and the subsequent occurrence of pancreatic cancer.

The study results revealed very interesting findings. At a global level, the total amount of oral microbes was similar between those who developed cancer and those who did not, but the microbial composition differed: certain species were much more abundant (or scarce) in the case group compared to the controls. In particular, three species of bacteria associated with gum disease stood out for their link with an increased risk of pancreatic cancer: Porphyromonas gingivalis, Eubacterium nodatum, and Parvimonas micra. These are known periodontal pathogens, implicated in chronic oral infections, and here it was observed that people with higher abundance of these “pyorrhea bacteria” in their mouths were more likely to develop pancreatic tumors.

This study also identified many other bacteria linked to risk: in total, they found 13 bacterial species whose elevated abundance was associated with higher likelihood of cancer, and 8 species whose presence was related to lower risk. Several of the bacteria associated with higher risk appear to be involved in metabolic processes, for example, in the breakdown of sugars and fats, which could favor an environment conducive to cancer in the pancreas. Taken together, these data reinforce the notion that poor oral health could contribute to the risk of pancreatic cancer through long-term inflammatory or infectious mechanisms.

One of the novel contributions of this work is that it not only examined bacteria but also oral fungi, where an incredible relationship was also found: the genus Candida (which includes common yeasts in the mouth) was significantly correlated with an increased risk of pancreatic cancer. Specifically, Candida tropicalis (an opportunistic yeast) was associated with higher risk, while Candida albicans (a very common species of Candida in the human mouth) was unexpectedly linked with lower risk, which means that not all fungi of this genus would have the same effect and reflects the complex dynamic in which certain fungal strains could be harmful and others perhaps protective. Most strikingly, researchers detected traces of Candida in the pancreatic tumor tissue of some patients, coinciding with the species present in their mouths; this suggests that these fungi could be physically reaching the pancreas (perhaps through the digestive tract) or at least creating an inflammatory environment favorable to the tumor, although a direct causal role cannot yet be confirmed.

Since multiple microbes associated with risk emerged, the scientific team developed a Microbial Risk Score (MRS). This score integrates the presence and abundance of 27 oral species identified as relevant (23 bacterial species and 4 fungal species) to provide each individual with a “risk profile” based on their oral microbiome. When applying this metric, they found that people with a high-risk microbial profile were more than three times more likely to develop pancreatic cancer compared to those with a low score.

Figure 1. Schematic representation of the association between oral microbiota and pancreatic cancer risk. Periodontal pathogens and fungi such as Candida tropicalis may contribute to systemic low-grade chronic inflammation, creating a tumor-promoting environment in the pancreas.

Although still an experimental tool, these results open the possibility that in the future a saliva test could be used as part of early detection: by identifying individuals with a “high-risk” microbiome, doctors could focus more intensive diagnostic tests on them in search of incipient pancreatic lesions.

Now, it is important to emphasize that correlation does not equal causation; the authors stress that their work identifies associations and does not prove that these microbes directly cause cancer, since the study was designed to detect links between disease risk and certain oral microbes, but not to establish a direct cause-and-effect relationship, which will require further research.

Main reference:

Meng Y, Wu F, Kwak S, et al. Oral Bacterial and Fungal Microbiome and Subsequent Risk for Pancreatic Cancer. JAMA Oncol. Published online September 18, 2025. https://jamanetwork.com/journals/jamaoncology/article-abstract/2839132

Other references:

Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H., & Jemal, A. (2025). Cancer statistics, 2025. CA: a cancer journal for clinicians, 75(1), 10–45. https://doi.org/10.3322/caac.21871

Stolzenberg-Solomon, R. Z., Dodd, K. W., Blaser, M. J., Virtamo, J., Taylor, P. R., & Albanes, D. (2003). Tooth loss, pancreatic cancer, and Helicobacter pylori. The American journal of clinical nutrition, 78(1), 176–181. https://doi.org/10.1093/ajcn/78.1.176

Herremans KM, Riner AN, Cameron ME, McKinley KL, Triplett EW, Hughes SJ, Trevino JG. The oral microbiome, pancreatic cancer and human diversity in the age of precision medicine. Microbiome. https://pmc.ncbi.nlm.nih.gov/articles/PMC9199224