Twenty-seven species of bacteria and fungi among the hundreds that live in people’s mouths have been collectively tied to a 3.5 times greater risk of developing pancreatic cancer, the results of a study led by NYU Langone Health and its Perlmutter Cancer Center have shown.
The researchers, headed by Yixuan Meng, PhD, a postdoctoral fellow in the Department of Population Health at NYU Grossman School of Medicine, carried out a prospective study, analyzing the genetic makeup of microbes collected from the saliva of 122,000 healthy men and women, and following participants to identify those who went on to develop pancreatic cancer over subsequent years.
The study results identified a combination of bacteria and fungi as a significant risk factor for pancreatic development. The team suggests that their findings point to oral microbiota as potential biomarkers of pancreatic cancer risk. The report is the largest and most detailed analysis of its kind to date, suggested Meng. It is also the first to show that oral fungi—more specifically, a yeast called Candida that naturally lives on the skin and throughout the body—may play a role in pancreatic cancer. The researchers also identified these oral Candida species in patients’ pancreatic tumors.
“Our findings provide new insight into the relationship between the oral microbiome and pancreatic cancer,” added Meng, who is co-senior author of the team’s published paper in JAMA Oncology, titled “Oral Bacterial and Fungal Microbiome and Subsequent Risk for Pancreatic Cancer.” In their paper, the investigators concluded, “The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention.”
Pancreatic cancer is highly lethal, with a five-year survival rate of 13%, the authors wrote. However, they pointed out, smoking, obesity, pancreatitis, and genetics, which are known risk factors, explain less than 30% of all pancreatic cancer, the authors wrote. “To reduce the pancreatic cancer burden, there is a critical need to improve scientific knowledge on the specific causes of this disease and to provide guidance for preventive measures.”
The oral microbiome, the diverse community of bacteria and fungi that inhabit the mouth, is increasingly being studied for its potential role in human health. Experts have long observed that those with poor oral health are more vulnerable to pancreatic cancer than those with healthier mouths. “There is strong evidence that microbially related poor oral health, and particularly periodontal disease, are risk factors for pancreatic cancer,” the team continued.
More recently, scientists have uncovered a mechanism that could help explain this connection, finding that bacteria can travel through swallowed saliva into the pancreas, an organ that helps with digestion. However, precisely which species may contribute to the condition had until now remained unclear.
Last year, the same team of scientists uncovered a link between certain oral bacteria and a heightened risk of developing head and neck squamous cell carcinoma, a group of cancers that arise in the mouth and throat. The researchers had also conducted a small study in 2016 that tied microbes living in the mouth to pancreatic cancer, but could not identify precise bacterial species.
For their newly reported study, the scientists assessed data from two ongoing investigations tracking Americans from across the country to better understand how diet, lifestyle, medical history, and many other factors are involved in cancer. The data were gathered for the American Cancer Society Cancer Prevention Study II and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
Shortly after enrolling, participants rinsed with mouthwash, providing saliva samples that preserved the numbers and species of microbes for testing. Researchers then followed up for roughly nine years on average to record any presence of tumors. They explained further, “We conducted a prospective study nested in two large well-established U.S. cohorts to determine whether the oral bacterial and fungal microbiome is associated with subsequent risk of pancreatic cancer, involving the use of whole-genome shotgun sequencing for oral bacteria and internal transcribed spacer (ITS) sequencing for fungi.”
The investigators identified 445 patients who were subsequently diagnosed with pancreatic cancer, and compared the DNA of these participants’ microbes with that of another 445 randomly selected study subjects who had remained cancer-free. The team made sure to account for factors known to play a role in developing the condition, such as age, race, and how often subjects smoked cigarettes.
The findings identified 24 species of bacteria and fungi that individually either raised or lowered pancreatic cancer risk. Another three kinds of bacteria tied to the cancer were already known to contribute to periodontal disease, a serious gum infection that can eat away at the jawbone and the soft tissues surrounding teeth.
Altogether, the entire group of microbes boosted participants’ chances of developing the cancer by more than threefold. “In this cohort study including 122,000 individuals, three oral bacterial periodontal pathogens, an additional 20 bacteria, and four fungi were identified, which together conferred a more than 3-fold increase in the risk for pancreatic cancer,” the investigators wrote in summary. In addition, by assessing the makeup of each participant’s oral microbiome, the scientists for the first time developed a tool that could estimate their cancer risk.
“By profiling bacterial and fungal populations in the mouth, oncologists may be able to flag those most in need of pancreatic cancer screening,” said study co-senior author Jiyoung Ahn, PhD, a professor in the Departments of Population Health and Medicine at NYU Grossman School of Medicine. The authors further suggested: “Collectively, the oral microbiome community may exert systemic effects on pancreatic cancer, with oral microbial dysbiosis contributing an etiological link between oral health status and pancreatic cancer development.”
Ahn, who is also the associate director for population sciences at Perlmutter Cancer Center, noted that there are currently few effective screening methods for the disease, which is among the deadliest forms of cancer. “It is clearer than ever that brushing and flossing your teeth may not only help prevent periodontal disease but may also protect against cancer,” said study co-senior author Richard Hayes, DDS, PhD, a professor in the Department of Population Health at NYU Grossman School of Medicine.
“These findings also underscore the potential importance of oral health interventions for prevention of pancreatic cancer,” the authors wrote. “The oral fungal and bacterial microbiotas may serve as readily accessible, noninvasive biomarkers for subsequent pancreatic cancer risk to identify individuals at high risk of pancreatic cancer.”
Hayes, who is also a member of Perlmutter Cancer Center, emphasized that the study was designed to identify correlations between disease risk and certain microbes in the mouth, but not to establish a direct cause-and-effect link. That will require further investigation.
The research team next plans to explore whether oral viruses could contribute to cancer and how the mouth’s microbiome may affect patients’ chances of survival, added Hayes.
