A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumours

What do we already know about this subject?

Cancer is one of the leading causes of death worldwide. The tumorigenesis, progression and treatment-response of cancer are influenced by various interactions between the immune system of the host and bacteria in the microbiota. However, the role of fungi (mycobiota) in these processes remains largely unexplored. Fungi and bacteria co-colonise the gastrointestinal tract, skin epithelium, airways and reproductive organs of mammals, forming a complex ecosystem of microbe-microbe and host-microbe interactions with significant implications for human health. While fungal infections account for over 1.5 million deaths worldwide each year, they only account for 0.1% of microbial DNA in the gut, suggesting a disproportionate influence of species from this kingdom on the overall gut microbiome and host immunity. Whether referring to viruses, bacteria or fungi, an ever growing body of scientific evidence suggests a link between the human microbiome and cancer and its outcomes. Several cases showing the association between bacterial species and cancer development/progression have been observed in recent years. Helicobacter pylori is responsible for approximately 75% of the risk attributable to gastric cancer, while genotoxic Escherichia coli, Bacteroides fragilis, Streptococcus bovis/gallolyticus and Fusobacterium nucleatum have been implicated in colorectal carcinogenesis [2]. The common feature of these bacteria is their ability to trigger chronic inflammation, a feature considered to contribute to their tumorigenic capacity. Recent reports have also identified intracellular bacteria in many types of tumour [3].

The mycobiome plays a key role in the activation of innate immunity in the gut. Mycotoxins and bioactive amines have been associated with carcinogenesis. Recent experimental studies support fungal involvement in cancer in some contexts [4]. Sequencing data from tumour banks have revealed the presence of microbial sequences, although the fungal component has not yet been explored.

What are the main insights from this study?

By analysing several types of cancer using “The Cancer Genome Atlas” (TCGA), the authors extracted tumour-associated mycobiome profiles with a species-level resolution. After eliminating contamination and false-positive signals, the authors reported that fungal compositions varied according to the type of cancer, and that some fungi were tumour-type specific, in both gastrointestinal and non-gastrointestinal locations (figure 1A). Overall, up to one fungal cell per 104 human tumour cells were observed, a rate consistent with the finding that fungi make up 0.1-1% of the microbiome, while bacteria are estimated to make up less than 1% of tumour cells [2, 3]. Abundant numbers of several species of Candida, Saccharomyces cerevisiae and Cyberlindnera jadinii have been found in gastrointestinal tumours, while Blastomyces and Malassezia species are abundant in lung and breast tumours, respectively. The authors then showed that several Candida species are alive and transcriptionally active in the tumour. Finally, the abundance of some fungi within the tumour could predict host tumour gene expression, disease status and survival (figure 1B), although these findings still need to be confirmed. Overall, these results suggest an involvement of fungi, especially Candida, in the pathogenesis of gastrointestinal cancers but also highlight their potential as a therapeutic target and prognostic tool.

What are the consequences in practice?

Alongside bacteria, this study reported the presence of fungi in many gastrointestinal and non-gastrointestinal tumours, with some degree of specificity across tumour types and a potential for predicting severity. These results suggest that fungi play a role in the cancer process and its severity. They could also pave the way for the development of new biomarkers or new cancer treatments targeting the fungal component.