Principal Investigator

Jiyoung
Ahn
Awardee Organization

New York University School Of Medicine
United States

Fiscal Year
2023
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

The Oral Mycobiome and Risk of Pancreatic Cancer

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.

Publications

  • Ahn J, Hayes RB. Environmental Influences on the Human Microbiome and Implications for Noncommunicable Disease. Annual review of public health. 2021 Apr 1;42:277-292. PMID: 33798404
  • Monson KR, Peters BA, Usyk M, Um CY, Oberstein PE, McCullough ML, Purdue MP, Freedman ND, Hayes RB, Ahn J. Elevated dietary carbohydrate and glycemic intake associate with an altered oral microbial ecosystem in two large U.S. cohorts. Cancer research communications. 2022 Dec;2(12):1558-1568. Epub 2022 Dec 5. PMID: 36567732
  • Usyk M, Pandey A, Hayes RB, Moran U, Pavlick A, Osman I, Weber JS, Ahn J. Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma. Genome medicine. 2021 Oct 13;13(1):160. PMID: 34641962
  • Um CY, Peters BA, Choi HS, Oberstein P, Beggs DB, Usyk M, Wu F, Hayes RB, Gapstur SM, McCullough ML, Ahn J. Grain, Gluten, and Dietary Fiber Intake Influence Gut Microbial Diversity: Data from the Food and Microbiome Longitudinal Investigation. Cancer research communications. 2023 Jan 11;3(1):43-53. doi: 10.1158/2767-9764.CRC-22-0154. eCollection 2023 Jan. PMID: 36968219
  • Peters BA, Yi SS, Beasley JM, Cobbs EN, Choi HS, Beggs DB, Hayes RB, Ahn J. US nativity and dietary acculturation impact the gut microbiome in a diverse US population. The ISME journal. 2020 Jul;14(7):1639-1650. Epub 2020 Mar 24. PMID: 32210364
  • Peters BA, Pass HI, Burk RD, Xue X, Goparaju C, Sollecito CC, Grassi E, Segal LN, Tsay JJ, Hayes RB, Ahn J. The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer. Genome medicine. 2022 Oct 27;14(1):121. PMID: 36303210
  • Kwak S, Usyk M, Beggs D, Choi H, Ahdoot D, Wu F, Maceda L, Li H, Im EO, Han HR, Lee E, Wu AH, Hayes RB, Ahn J. Sociobiome - Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US. NPJ biofilms and microbiomes. 2024 Mar 11;10(1):19. PMID: 38467678
  • Ahn J, Kwak S, Usyk M, Beggs D, Choi H, Ahdoot D, Wu F, Maceda L, Li H, Im EO, Han HR, Lee E, Wu A, Hayes R. Sociobiome - Individual and neighborhood socioeconomic status influence the gut microbiome in a multi-ethnic population in the US. Research square. 2023 Apr 19. PMID: 37131763