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Mycobiome and Cancer
Although comprising a much smaller proportion of the human microbiome, the fungal community has gained much more attention lately due to its multiple and yet undiscovered interactions with the human bacteriome and the host. Head and neck cancer carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma have been associated with dissimilarities in the composition of the mycobiome between cases with cancer and non-cancer subjects. In particular, an abundance of Malassezia has been associated with the onset and progression of colorectal carcinoma and pancreatic adenocarcinoma, while the genera Schizophyllum, a member of the oral mycobiome, is suggested to exhibit anti-cancer potential. The use of multi-omics will further assist in establishing whether alterations in the human mycobiome are causal or a consequence of specific types of cancers.
2. Mycobiome and Head and Neck Cancer
|Research/Year||Population, Type of Study||Clinical Specimen||Main Findings||Remarks|
|Head and Neck Cancer|
|Perera et al., 2017 ||52 individuals; 25 with OSCC; 27 intra-oral-fibro epithelial polyps||52 biopsies from 25 patients with OSCC and 27 with oral polyps. DNA was extracted and sequenced for the ITS2 region||364 species accounting for 160 genera and 2 phyla (Ascomycota and Basidiomycota) were detected.
Candida and Malassezia made up 48% and 11% of the average fungal community, respectively, according to Luan et al., 2015.
|-5 species and 4 genera were identified in more than half of samples.
-Less abundance and diversity in OSCC tissues of patients.
-Candida, Hannaella, and Gibberella were ↑↑ in OSCC; Altenaria and Trametes were in greater quantity in polyps specimens.
-Candida albicans, Candida etchellsii, and Hannaella luteola–like species were enriched in OSCC Hanseniaspora uvarum–like species, Malassezia restricta, and Aspergillus tamarii are predominant in polyps specimens.
-Dysbiotic mycobiome dominated by C. albicans has been observed in OSCC.
|Mukherjee et al., 2017 ||39 participants with OSCC of the tongue||39 tissue samples from oral SCC and adjacent tissues were analyzed after DNA extraction for 16S/18S rRNA gene.||Fungal richness was ↓↓ in tumor tissue (TT) in comparison to the adjacent non-cancerous tissue (ANCT), p < 0.006.
The presence of 22 bacterial and 7 fungal genera was different in TT and ANCT.
Aspergillus in TT was negatively associated with the presence of bacteria Actinomyces, Prevotella, Streptococcus, whilst it presented a positive association with Aggregatibacter.
|-Subjects with advanced T-stage disease presented reduced mean differences between TT and ANCT, in comparison to subjects with regional disease.
-Findings indicative of differences in the bacteriome and mycobiome between OSCC patients and their adjacent non-cancerous oral epithelium
-Association with T-stage.
-Despite the similarities in the index of diversity of the mycobiome between TT and ANCT, the abundance of the mycobiome was diminished in TT.
-This study is suggestive of existing changes in the local environment in patients with OSCC, expressed as specific bacterial and fungal dysbiosis
|Vesty et al., 2018 ||30 participants, including 14 patients with HNSCC||Saliva specimens analyzed by 16S rRNA gene and ITS1amplicon sequencing||↑↑ Candida
Candida albicans representing more than 96% of fungi in the majority of subjects with HNSCC.
|-↑↑ IL-1β and IL-8 in HNSCC and patients with poor dental health, when compared to healthy controls.
-IL-1β and IL-8 levels were associated with C. albicans.
-In HNSCC, salivary microbial and inflammatory markers are affected by oral hygiene.
|Shay et al., 2020 ||92 individuals, including 46 patients with HNSCC||Oral wash samples analyzed by 16S rRNA and ITS gene sequencing||Distinct strains of Candida albicans are increased or decreased in oral wash specimens from patients with HNSCC, when compared to healthy controls.||-Distinct strains of Candida albicans and Rothia mucilaginosa differed in numbers. Schizophyllum commune was decreased in HNSCC patients, in comparison to healthy controls.
-Compared to controls, oral cavity of subjects with HNSCC presents distinct differences in the mycobiome and bacteriome, and their interactions.
|Luan et al., 2015 ||27 patients with colorectal adenomas||Biopsies from colorectal adenomas and adjacent tissues were studied by using denaturing gradient gel electrophoresis (DGGE)||↑↑ Ascomycota, Glomeromycota and Basidiomycota.
↓↓ diversity in adenomas compared to adjacent tissue
|-↑↑ Basidiomycota in adjacent tissues.
-↑↑ Basidiomycota and Saccharomycetales in advanced adenoma samples, when compared to non-advanced.
|Gao et al., 2017 ||131 individuals with colorectal carcinoma (CRC), colorectal polyps and normal subjects||Stool samples from patients with CRC, polyps and normal subjects were analyzed by using ITS2 gene sequencing||↑ ↑ Ascomycota followed by Basidiomycota
↓↓ diversity in the polyp group, when compared to controls.
|↑↑ Ratio of Ascomycota to Basidiomycota in subjects with CRC and polyps, in comparison to controls.
↑↑ of the opportunistic fungi Trichosporon and Malassezia, which could be implicated in the progression to CRC.
|Richard et al., 2018 ||27 patients with CRC; 7 with colitis-associated cancer, 10 patients with sporadic cancer and 10 healthy individuals||Tissue specimens from colonic resections in colitis-associated malignancy and sporadic CRC groups were analyzed using 16S rRNA and ITS2 sequencing||↑↑ Basidiomycota followed by Ascomycota
↓ diversity in sporadic cancer.
|↑↑ Basidiomycota in colitis-associated cancer.|
|Coker et al., 2019 ||585 individuals; 184 patients with CRC, 197 patients colorectal adenomas and 204 normal subjects||Stool samples from patients with CRC, colorectal adenomas and normal subjects were analyzed by fecal shotgun metagenomic sequencing||-Ascomycota, Basidiomycota and Mucoromycota in patients with CRC and healthy participants.
-No difference in diversity
|-↑↑ Basidiomycota/Ascomycota ratio in CRC when compared to controls.
-14 fungi identified with differential composition between CRC and controls.
|Aykut et al., 2019 ||(1) Experiments in mice as well as in humans using 18S rRNA sequencing
KC mice, which develop spontaneous pancreatic cancer by targeted expression of mutant Kras. C57BL/6, MBL-null, and C3−/− mice.
(2) Human stool samples and pancreatic tissue specimens were gathered from healthy volunteers and subjects undergoing surgery for PDA or benign pancreatic disorder.
|Because of the direct proximity and relationship of the intestinal and pancreatic duct via the Oddi sphincter, gut fungi could enter the pancreas. To examine this hypothesis, they administered GFP-labeled Saccharomyces cerevisiae to controls or cancer-bearing mice through oral gavage. Fungi moved into the pancreas in less than thirty minutes, suggesting that the intestinal fungal community may directly impact on the pancreatic microenvironment.||-PDA tumors harbored a ~3000-fold augmentation in fungi, in comparison to physiologic pancreas in both mice and humans.
-PDA mycobiome was different from gut or physiologic pancreatic mycobiome based on diversity indexes.
-The fungal community infiltrating PDA was ↑↑ enriched in Malassezia in mice and humans.
-Fungal elimination with the use of amphotericin B was tumor-protective in slowly progressive as well as in models of invasive PDA, whereas re-population with Malassezia but not Candida, Saccharomyces, or Aspergillus–promoted oncogenesis.
|-Connection of mannose-binding lectin (MBL), that attaches fungal wall glycans to activate the complement pathway, was needed in the promotion of malignancy.
-MBL or C3 deletion in the extra-tumoral area or C3aR knockdown in tumor cells prevented tumor expansion. Reprogramming of the fungal ecosystem did not change PDA progression in MBL or C3 deficient mice.
-Pathogenic fungi may promote PDA by activating the complement pathway via MBL induction.
3. Mycobiome and Colorectal Cancer (CRC)
3.1. The Role of Fungal Dysbiosis in CRC
The entry is from 10.3390/cancers13133149
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