Oral mycobiota and pancreatic ductal adenocarcinoma

Abstract

Early detection of pancreatic ductal adenocarcinoma (PDAC) is essential for survival. Preliminary research demonstrated significant associations between structural alternation of mycobiota and PDAC. In this study, we investigated the associations between oral mycobiota and PDAC. We further explored mycobiota biomarkers for PDAC detection. We enrolled 34 PDAC patients and 35 matched healthy controls from West China hospital in Southwest China. Demographic data, clinical information, and salivary samples were collected. Mycobiota characteristics were defined using Internal Transcribed Spacer (ITS) ribosomal RNA sequencing. We found that the PDAC patients had significant increase in fungal abundance (P < 0.001) and significant decrease in fungal diversity (P < 0.001) in comparison to the healthy controls. A higher abundance of Basidiomycota and Unclassifed_p_Ascomycota was associated with an increased risk of PDAC. With each increase of abundance of g__unclassified_k__Fungi and g__unclassified_p__Ascomycota in PDAC patients, the risk of pancreatic cancer increased by 1.359 odds and 1.260 odds, respectively. Aspergillus (AUC = 0.983, 95% CI 0.951–1.000) and Cladosporium (AUC = 0.969, 95% CI 0.921–1.000) achieved high classification powers to distinguish PDAC patients from the healthy controls. The rapid, inexpensive tests of ITS1 sequencing of mycobiota and PCR detection of potential fungal biomarkers make it promising for the clinical practice to use oral microbes for PDAC early detection and prevention. Results of our study provide evidence that salivary mycobiota may provide insights into cancer risk, prevention, and detection.

Fungi and cancer

“…Higher levels of Malassezia were also positively associated with overall survival in OSCC patient saliva samples 161. Saliva mycobiome assessment by ITS sequencing demonstrated a higher fungal abundance and a lower alpha diversity in patients with PDAC compared with healthy controls 162 163 . Aspergillus and Cladosporium emerged as leading differentiators between tumour bearing patients and healthy controls, meriting future studies.…”

Microbiota and mycobiota in bronchoalveolar lavage fluid of silicosis patients

“…The 16S rRNA gene was amplified using barcoded 338 F:5′-ACTCCTACGGGAGGCAGCA-3′ and 806R:5’-GGACTACHVGGGTWTCTAAT-3’ [ 33 ]. The ITS1 gene was amplified using barcoded ITS1 5F:5′-GGAAGTAAAAGTCGTAACAAGG-3′ and ITS1 2R:5′-GCTGCGTTCTTCATCGATGC-3′ [ 27 , 34 ]. DNA libraries were constructed according to protocol described in a previous study [ 35 ].…”

Roles of microbiota in pancreatic cancer development and treatment

“…took advantage of Internal Transcribed Spacer (ITS) rRNA sequencing to further characterize the mycobiota in saliva samples from PDAC patients. 40 Decreased alpha diversity was found in PDAC patients compared to healthy controls. The taxa Aspergillus and Cladosporium were not only less abundant in PDAC but also presented high classification power to discriminate between both groups.…”

“…The taxa Aspergillus and Cladosporium were not only less abundant in PDAC but also presented high classification power to discriminate between both groups. 40 However, the study of the mycobiota in PDAC is still in its early stages, and further research is required to solidify this link.…”