The Oral Mycobiome and Risk of Pancreatic Cancer

ABSTRACT
We hypothesize that oral fungi potentiate pancreas carcinogenesis via the pancreas tumor immune
microenvironment. The human oral cavity hosts a diverse microbiota, including bacteria and fungi. Our team has
made novel findings that human oral bacterial microbiome is related to risk of pancreas cancer development. In
this proposal, we focus on oral fungi (the mycobiome), a “keystone” component of the oral microbiome with the
highest biomass. Clinical candidiasis and carriage of a rare candidiasis-related genetic disorder increase risk for
pancreas cancer. In our preliminary data, we made novel finding that specific oral fungi are associated with at
least 2-fold differentials in pancreatic cancer risk, and those fungi are found in pancreas tumor tissue. We recently
reported that fungi experimentally promote pancreas cancer and tumoral immune response in animals. Taken
together, these data strongly support our hypothesis.
Our ultimate goal is to identify specific oral fungal microbiota in the general population that may be managed to
prevent pancreatic cancer. Our specific aims are: 1) to test whether oral fungal microbiome is associated with
subsequent risk of pancreatic cancer in a nested case-control study and 2) to test the hypothesis that
metabolically active fungi in the pancreas influence tumor immunity. Strengths of this study include a large
prospective study design, with oral samples collected prior to cancer development, and state-of-the-art fungal
and immune phenotype assays that will accurately and comprehensively characterize fungal composition and
immune phenotypes. This is the first investigation of oral and pancreas fungal microbiome and pancreatic cancer
risk.
Pancreatic cancer is highly lethal and little is known about ways to detect and prevent this disease. We expect
to identify specific oral fungi associated with risk of pancreas cancer and to identify fungal—host pancreatic
tumor immune response. These outcomes will expand our current limited knowledge on the causes of pancreatic
cancer, will help to identify people at high risk for this disease, and may lead to microbial-based prophylactic
prevention for pancreatic cancer. Thus, findings may help to rapidly advance our ability to reduce the burden of
this highly fatal disease.

Grant Number: 5U01CA250186-04
NIH Institute/Center: NIH
Principal Investigator: Jiyoung Ahn