The gastrointestinal mycobiome in inflammation and cancer: unraveling fungal dysbiosis, pathogenesis, and therapeutic potential.

Abstract

The gastrointestinal mycobiome, comprising diverse fungal species, plays a significant role in gastrointestinal carcinogenesis and inflammatory bowel disease (IBD) pathogenesis. Recent studies have demonstrated that dysbiosis of the gut mycobiome, characterized by an overrepresentation of pathogenic fungi such as Candida albicans and Aspergillus, correlates with increased inflammation and cancer risk. For instance, C. albicans has been shown to induce colonic inflammation through the activation of pattern recognition receptors and the release of pro-inflammatory cytokines, exacerbating IBD symptoms and potentially facilitating tumorigenesis. Additionally, metagenomic analyses have revealed distinct fungal signatures in colorectal cancer tissues compared to adjacent healthy tissues, highlighting the potential of fungi as biomarkers for disease progression. Mechanistically, gut fungi contribute to disease through biofilm formation, mycotoxin secretion (e.g., aflatoxins, candidalysin), pro-inflammatory cytokine induction (e.g., IL-1β, IL-17), and disruption of epithelial barriers-creating a tumor-promoting and inflammation-prone environment. Furthermore, the interplay between fungi and the bacterial microbiome can amplify inflammatory responses, contributing to chronic inflammation and cancer development. Fungal interactions with bacterial communities also play a synergistic role in shaping mucosal immune responses and enhancing disease severity in both cancer and IBD contexts. As research continues to elucidate these complex fungal-host and fungal-bacterial interactions, targeting the gut mycobiome may offer novel therapeutic avenues for managing IBD and gastrointestinal cancers, emphasizing the need for integrated, mechanistically informed approaches to microbiome research.