Fungal Microbiota Dysbiosis and Ecological Alterations in Gastric Cancer

Abstract

Changes in bacteriome composition have a strong association with gastric cancer (GC). However, the relationship between stomach fungal microbiota composition and human host immune factors remains largely unknown. With high-throughput internal transcribed spacer region 2 (ITS2) sequencing, we characterized gastric fungal microbiome among the GC (n = 22), matched para-GC (n = 22), and healthy individuals (n = 11). A total of 4.5 million valid tags were generated and stratified into 1,631 operational taxonomic units (OTUs), and 10 phyla and 301 genera were identified. The presence of GC was associated with a distinct gastric fungal mycobiome signature, characterized by a decreased biodiversity and richness and significant differences in fungal composition. In addition, fungal dysbiosis was reflected by the increased ratio of Basidiomycota to Ascomycota and a higher proportion of opportunistic fungi, such as Cutaneotrichosporon and Malassezia, as well as the loss of Rhizopus and Rhodotorula during the progression of cancers. A panel of GC-associated fungi (e.g., Cutaneotrichosporon and Rhodotorula) was found to adequately exhibit diagnostic value. Furthermore, the mRNA levels of cytokines and chemokines were detected and correlated with the specific fungal dysbiosis, indicating the possible mechanism of GC. This study reveals GC-associated mycobiome dysbiosis characterized by altered fungal composition and ecology and suggests that the fungal mycobiome might play a role in the pathogenesis of GC.

Mycobiota and C-Type Lectin Receptors in Cancers: Know thy Neighbors

“…(A) Shay et al (2020) demonstrated the differences of the mycobiome in the oral washings from patients with head and neck squamous cell carcinoma (HNSCC) compared to matched control participants; Mukherjee et al (2017) revealed the differences of the mycobiome in the tumor tissues compared to adjacent non-tumor tissues from patients with oral squamous cell carcinoma OSCC (mobile) in the tongue. (B) Zhong et al (2021) and Zhang et al (2022) revealed the differences of the mycobiome in the tumor tissues compared to adjacent non-tumor tissues from patients with gastric cancer; Yang et al (2022) revealed the differences of the mycobiome in the tumor tissues from patients with gastric cancer compared to normal tissue from healthy controls. (C) Coker et al (2019) and Gao et al (2022) revealed the differences of the mycobiome in the stool samples from patients with colorectal cancer compared to healthy controls.…”

“…Another study was not entirely consistent with these results, as it found no significant difference in alpha and beta diversity between the GC and the matched para-GC groups. However, the results also indicated that compared to gastric tissue from healthy populations, GC tissue had significantly lower alpha diversity of fungi, and the GC group also formed a relatively well-separated fungal flora ( Yang et al, 2022 ). Furthermore, fungal dysbiosis was reflected by a higher proportion of opportunistic fungi, such as Cutaneotrichosporon and Malassezia in patients with GC compared to healthy controls ( Yang et al, 2022 ; Figure 1B ).…”

“…However, the results also indicated that compared to gastric tissue from healthy populations, GC tissue had significantly lower alpha diversity of fungi, and the GC group also formed a relatively well-separated fungal flora ( Yang et al, 2022 ). Furthermore, fungal dysbiosis was reflected by a higher proportion of opportunistic fungi, such as Cutaneotrichosporon and Malassezia in patients with GC compared to healthy controls ( Yang et al, 2022 ; Figure 1B ). The receiver operating characteristic (ROC) curves showed great diagnostic potential in distinguishing GC and healthy controls, including Cystobasidium, Cutaneotrichosporon, Apiotrichum, Simplicillium, Lecanactis, Rhizopus, Rhodotorula, Exophiala , and Sarocladium ( Yang et al, 2022 ).…”

“…Furthermore, fungal dysbiosis was reflected by a higher proportion of opportunistic fungi, such as Cutaneotrichosporon and Malassezia in patients with GC compared to healthy controls ( Yang et al, 2022 ; Figure 1B ). The receiver operating characteristic (ROC) curves showed great diagnostic potential in distinguishing GC and healthy controls, including Cystobasidium, Cutaneotrichosporon, Apiotrichum, Simplicillium, Lecanactis, Rhizopus, Rhodotorula, Exophiala , and Sarocladium ( Yang et al, 2022 ). Similar to the above study by Yang et al (2022) , Zhang et al (2022) discovered no significant difference in fungal diversity between tumor and paracancerous tissues.…”

“…The receiver operating characteristic (ROC) curves showed great diagnostic potential in distinguishing GC and healthy controls, including Cystobasidium, Cutaneotrichosporon, Apiotrichum, Simplicillium, Lecanactis, Rhizopus, Rhodotorula, Exophiala , and Sarocladium ( Yang et al, 2022 ). Similar to the above study by Yang et al (2022) , Zhang et al (2022) discovered no significant difference in fungal diversity between tumor and paracancerous tissues. Furthermore, they demonstrated that Solicoccozyma and Solicoccozyma aeria were significantly enriched in the tumor tissue ( Figures 1B , 2B ).…”