A groundbreaking study led by researchers at NYU Langone Health and its Perlmutter Cancer Center has unveiled compelling evidence linking the composition of the oral microbiome—the diverse ecosystem of bacteria and fungi residing within the human mouth—to an increased risk of pancreatic cancer. Through meticulous genetic analysis of saliva-derived microbes from an immensely large cohort of over 122,000 healthy individuals, the research team identified twenty-seven distinct species of bacteria and fungi collectively associated with a 3.5-fold heightened risk of developing this notoriously lethal cancer. These findings, recently published in JAMA Oncology, mark a significant advance in understanding the microbial factors that may underlie pancreatic tumorigenesis, a disease that remains among the most challenging to detect and treat effectively.
For decades, epidemiologists and clinicians have noted a correlation between poor oral health—characterized by chronic gum inflammation and periodontal disease—and increased vulnerability to pancreatic cancer. Yet the precise microbial culprits and biological pathways mediating this association have remained elusive. This new investigation addresses those gaps by adopting an integrative approach to profile the oral microbiome through cutting-edge genomic sequencing technologies. Saliva samples, collected from participants shortly after enrollment in two extensive, nationwide longitudinal studies—the American Cancer Society Cancer Prevention Study II and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial—were analyzed to decode the bacterial and fungal DNA signatures and identify microbial patterns predictive of future malignancy.
Importantly, the study not only confirmed the role of certain pathogenic bacteria previously implicated in periodontal disease but also for the first time pinpointed oral fungi, particularly Candida species, as potentially influential contributors to pancreatic carcinogenesis. Laboratory analyses revealed the presence of Candida DNA within pancreatic tumor tissues, suggesting a possible translocation route whereby microorganisms from the oral cavity may migrate and influence tumor microenvironments in distant organs. This raises provocative questions about the mechanisms of microbial trafficking and microbial-host interactions that might facilitate the initiation or progression of pancreatic tumors.
Methodologically, the research employed an observational design, leveraging matched case-control comparisons to robustly associate specific microbial fingerprints with pancreatic cancer incidence. Of the cohort, 445 individuals were diagnosed with pancreatic cancer during an average nine-year follow-up, and their oral microbial profiles were contrasted against 445 cancer-free counterparts. To ensure rigor, the analysis adjusted for confounding variables including demographic factors such as age and race, and behavioral risks like cigarette smoking frequency, thereby isolating the effect attributed to the oral microbiome. This approach underlines the robustness of the observed associations and diminishes the likelihood that the findings are artifacts of external influences.
The intricate web of interactions within the oral microbiome is a burgeoning field of research with profound implications. This study contributes to it by demonstrating that microbial communities in the mouth constitute a potential biomarker reservoir for systemic diseases far beyond traditional dental concerns. The discovery that a composite of bacteria and fungi engenders more than a threefold increase in pancreatic cancer risk underscores the need to perceive oral health as a critical determinant of overall human health and a gateway organ influencing distant pathologies.
Novel techniques employed included next-generation sequencing to capture a comprehensive catalog of microbial species, coupled with advanced bioinformatics analyses to quantify microbial load and diversity. These technical advancements allowed the research team to discern individual bacterial and fungal species that either heightened or diminished pancreatic cancer risk, offering an unprecedented granularity in microbial epidemiology. It also facilitated the construction of a predictive risk assessment tool based on the oral microbiome’s composition, presenting a potential clinical application where oncologists could stratify patients for early pancreatic cancer screening—a critical breakthrough given the paucity of effective early detection methods currently available for this malignancy.
Senior investigators emphasize the translational potential of these findings. “Profiling the bacterial and fungal populations inhabiting the oral cavity paves a new path for identifying individuals at elevated risk for pancreatic cancer, offering an opportunity to intervene earlier and improve survival outcomes,” remarked Dr. Jiyoung Ahn, co-senior author of the study and a professor specializing in population health and medicine at NYU Grossman School of Medicine. The research team’s next phase aims to investigate whether viral components of the oral microbiome similarly influence cancer risk and to explore how these microbial ecosystems might affect responses to treatment and overall patient prognosis.
The mechanistic insights suggested by this research invite a reevaluation of the permeability and immunological interfaces between the gastrointestinal tract and systemic circulation. Microbial translocation pathways, perhaps facilitated by swallowing or microaspiration of saliva containing opportunistic pathogens, may introduce microbial antigens or induce inflammatory cascades in pancreatic tissues, fostering an environment conducive to neoplastic transformation. The identification of fungal species such as Candida highlights the role of fungal-bacterial cohabitation and potential synergistic effects in tumor biology—areas ripe for deeper molecular investigation.
While the study was designed to uncover correlations rather than establish causation, it lays a critical foundation for future interventional studies. Before definitive causal links can be confirmed, experimental models elucidating the effect of specific oral microbes on pancreatic cell transformation and growth are necessary. Nevertheless, the robust association and biological plausibility illuminated by this massive data-driven study underscore oral hygiene’s broader impact beyond local infections. The researchers underscore the importance of public health messaging reinforcing the need for diligent oral care habits—brushing, flossing, and dental check-ups—as part of an integrative approach to cancer prevention.
Funding support for this ambitious work came from multiple National Institutes of Health grants, reflecting its significance and the cross-disciplinary collaboration among epidemiologists, microbiologists, oncologists, and bioinformaticians. The research team comprises experts not only from NYU Langone Health but also collaborators from Albert Einstein College of Medicine, the National Cancer Institute, and the American Cancer Society, highlighting the collective effort required to tackle such a complex biomedical challenge.
NYU Langone Health’s reputation as a leading integrated health system frames this study within a context of clinical excellence and innovation. With state-of-the-art facilities and a commitment to translating molecular discoveries into improved patient care, the institution continues to push boundaries in understanding how the human microbiome intersects with cancer risk. This study exemplifies the cutting-edge research vital to developing personalized medicine strategies that could revolutionize pancreatic cancer screening and potentially transform outcomes for a disease traditionally diagnosed too late.
In sum, by charting the uncharted territory of fungal involvement alongside bacterial influences within the oral microbiome, this landmark study opens novel investigative avenues and compels the medical community to consider the mouth as a sentinel site for cancer risk assessment. With future research poised to clarify microbial causality and intervention strategies, the promise of integrating oral microbiome profiling into standard oncological practice may become a tangible reality. As it stands, this research offers hope for early identification of individuals at risk and highlights a surprising nexus between everyday oral microbes and one of the deadliest cancers globally.
Subject of Research: People
Article Title: Oral Bacterial and Fungal Microbiome and Subsequent Risk for Pancreatic Cancer
News Publication Date: 18-Sep-2025
Web References: https://doi.org/10.1001/jamaoncol.2025.3377
References: National Institutes of Health grants P30CA016087, P20CA252728, R01LM014085, R01CA159036, and U01CA250186
Keywords: Pancreatic cancer, Human microbiota, Fungi, Bacteria, Bacterial DNA
