Micro- and Mycobiota Dysbiosis in Pancreatic Ductal Adenocarcinoma Development

Bellotti, Ruben; Speth, Cornelia; Adolph, Timon E.; Lass‐Flörl, Cornelia; Effenberger, Maria; Öfner, Dietmar; Maglione, Manuel

doi:10.3390/cancers13143431

“…The skin commonly has a large population of gram-positive bacteria, but recent 16S sequencing has revealed that there is a smaller population of gram-negative bacteria present specifically proteobacteria [ 60 ]. Proteobacteria were found to be present more so in patients with PDAC tumors than healthy individuals [ 61 ]. Aykut et al have found that PDAC tumors were enriched for Malassezia species and there was a significant loss of others such as the Candida and Saccharomyces species.…”

Section: The Microbiome Influences Pancreatic Cancer Developmentmentioning

confidence: 99%

Connecting the Human Microbiome and Pancreatic Cancer

Sexton

¹

,

Uddin

²

,

Bannoura

³

et al. 2022

Cancer Metastasis Rev

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Pancreatic cancer is a deadly disease that is increasing in incidence throughout the world. There are no clear causal factors associated with the incidence of pancreatic cancer; however, some correlation to smoking, diabetes and alcohol has been described. Recently, a few studies have linked the human microbiome (oral and gastrointestinal tract) to pancreatic cancer development. A perturbed microbiome has been shown to alter normal cells while promoting cancer-related processes such as increased cell signaling, immune system evasion and invasion. In this article, we will review in detail the alterations within the gut and oral microbiome that have been linked to pancreatic cancer and explore the ability of other microbiomes, such as the lung and skin microbiome, to contribute to disease development. Understanding ways to identify a perturbed microbiome can result in advancements in pancreatic cancer research and allow for prevention, earlier detection and alternative treatment strategies for patients.

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“…Malassezia has a higher abundance in colorectal cancer (CRC) compared to the colon polyp. Gut-derived Malassezia 13 Journal of Immunology Research globosa markedly enriches in both mice and human pancreatic ductal adenocarcinoma cancer (PDAC) and promotes pancreatic oncogenesis by driving the complement cascade through the activation of MBL [29,30]. In addition to the Malassezia-associated CRC and PDAC, we focused on GC and immune-suppressive checkpoint, revealing the association of Malassezia globosa and PD-L1 expression in the GC microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Identification of Malassezia globosa as a Gastric Fungus Associated with PD-L1 Expression and Overall Survival of Patients with Gastric Cancer

Zhang

¹

,

Qiu

²

,

Feng

³

et al. 2022

Journal of Immunology Research

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Background. Microbiotas affected the prognosis of cancer patients by regulating programmed death ligand-1 (PD-L1) expression. However, the relationship between gastric fungi and PD-L1 expression is still unclear in gastric cancer (GC). We aimed at exploring the association of gastric fungi with PD-L1 expression and overall survival in GC. Methods. A total of 61 GC patients were divided into the two groups based on the PD-L1 combined positive scores (CPS). Fungal profiling was performed by internal transcribed spacer rDNA sequencing, and the survival analyses were performed by Kaplan-Meier curves. Results. We observed a taxonomic difference of fungi between the PD-L1-High ( C P S ≥ 10 ) and PD-L1-Low group ( C P S < 10 ) by principal coordinates analysis (PCoA) ( P = 0.014 for Bray-Curtis and P = 0.042 for Jaccard). Malassezia had a higher abundance in the PD-L1-High group compared to the PD-L1-Low group ( P = 0.045 ). Malassezia globosa elevated significantly in the PD-L1-High group. GC patients with PD-L1 low expression and low abundance of Malassezia globosa had a longer overall survival (OS) than others ( P = 0.047 ). Malassezia globosa was associated with PD-L1 expression ( O d d s R a t i o = 3.509 , 95% Confidence Interval: 1.056-11.656, P = 0.040 ). Malassezia globosa was associated with the tumor size ( P = 0.031 ) and PD-L1 status ( P = 0.024 ). GC patients with a high abundance of Malassezia globosa had shorter OS than others ( P = 0.028 ). Malassezia globosa was an independent factor ( H a z a r d R a t i o = 3.080 , 95% Confidence Interval: 1.140-8.323, P = 0.027 ) for OS after adjusting for tumor stage. Malassezia globosa was figured out to be associated with- fatty acid and lipid biosynthesis and degradation via LIPASYN pathway. Conclusions. Malassezia globosa was identified as a PD-L1 expression-associated gastric fungus and associated with OS of GC patients, which calls for more studies to further explore its potential in PD-L1/PD-1 targeted immunotherapy.

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“…Similarly, an Asian cohort study conducted in Taiwan found that Candida-infected individuals have a higher risk of PDAC [17]. Mycobiome, especially pathogenic fungi, can stimulate PDAC by driving the complement cascade through mannose-binding lectin (MBL) activation [3,18,19], while the genera Schizophyllum, a member of the oral mycobiota, showed potential anti-cancer function [20]. Nevertheless, the role of oral mycobiota in the onset and progression of PDAC has not been comprehensively investigated [2].…”

Section: Introductionmentioning

confidence: 99%

Oral mycobiota and pancreatic ductal adenocarcinoma

Wei

¹

,

Zhao

²

,

Xue

³

et al. 2022

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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.

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Micro- and Mycobiota Dysbiosis in Pancreatic Ductal Adenocarcinoma Development

Cited by 22 publications

References 104 publications

Connecting the Human Microbiome and Pancreatic Cancer

Connecting the Human Microbiome and Pancreatic Cancer

Identification of Malassezia globosa as a Gastric Fungus Associated with PD-L1 Expression and Overall Survival of Patients with Gastric Cancer

Oral mycobiota and pancreatic ductal adenocarcinoma

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