Candida albicans disorder is associated with gastric carcinogenesis

Abstract

Background: Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal microbiome in GC. Methods: We performed ITS rDNA gene analysis in cancer lesions and adjacent noncancerous tissues of 45 GC cases from Shenyang, China. Obtaining the OTUs and combining effective grouping, we carried out species identifications, alpha and beta diversity analyses, and FUNGuild functional annotation. Moreover, differences were compared and tested between groups to better investigate the composition and ecology of fungi associated with GC and find fungal indicators. Results: We observed significant gastric fungal imbalance in GC. Principal component analysis revealed separate clusters for the GC and control groups, and Venn diagram analysis indicated that the GC group showed a lower OTU abundance than the control. At the genus level, the abundances of 15 fungal biomarkers distinguished the GC group from the control, of which Candida ( p = 0.000246) and Alternaria ( p = 0.00341) were enriched in GC, while Saitozyma ( p = 0.002324) and Thermomyces ( p = 0.009158) were decreased. Combining the results of Welch's t test and Wilcoxon rank sum test, Candida albicans ( C. albicans ) was significantly elevated in GC. The species richness Krona pie chart further revealed that C. albicans occupied 22% and classified GC from the control with an area under the receiver operating curve (AUC) of 0.743. Random forest analysis also confirmed that C. albicans could serve as a biomarker with a certain degree of accuracy. Moreover, compared with that of the control, the alpha diversity index was significantly reduced in the GC group. The Jaccard distance index and the Bray abundance index of the PCoA clarified separate clusters between the GC and control groups at the species level ( p = 0.00051). Adonis (PERMANOVA) analysis and ANOVA showed that there were significant differences in fungal structure among groups ( p = 0.001). Finally, FUNGuild functional classification predicted that saprotrophs were the most abundant taxa in the GC group. Conclusions: This study revealed GC-associated mycobiome imbalance characterized by an altered fungal composition and ecology and demonstrated that C. albicans can be a fungal biomarker for GC. With the significant increase of C. albicans in GC, the abundance of Fusicolla acetilerea, Arcopilus aureus, Fusicolla aquaeductuum were increased, while Candida glabrata, Aspergillus monte...

The role of gut mycobiome in health and diseases

“…Indeed, recent study reveals a perturbation of fungal compositional and ecological changes in gastric cancer development and C. albicans was characterized as a biomarker for gastric cancer. 98 Given that early life factors are known to influence host microbiome status, data on early life gut mycobiome and factors influencing their development were reviewed.…”

Mycobiota dysbiosis and gastric tumorigenesis

“…The importance of the mycobiota in gastrointestinal cancer development is poorly understood, though recent studies implicate gut fungi in pancreatic, oesophageal, and colonic oncogenesis 4 - 7 . In this issue of Theranostics , Zhong and colleagues report an association between mycobiota dysbiosis and GC 8 (Figure 1 ).…”

Microbiome and cancer

“…Mechanistically, Malassezia migrates to the pancreas and activates the complement cascade via the binding of host mannose-biding lectins to fungal cell walls (Aykut et al, 2019). Recently, an outgrowth of Candida albicans was associated with, and suggested to be even predictive of, gastric cancers (Zhong et al, 2021). Several putative mechanisms may causally link C. albicans and cancer risk, including production of nitrosamines, which are known to alter cell proliferation in oral cancers (Sanjaya et al, 2011), induction of immune modulation via TNFa and IL-18, and promotion of tumor cell adhesion to epithelial cells (Ramirez-Garcia et al, 2013).…”