The gut mycobiome and metabolic dysfunction in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) affects approximately 589 million adults globally, yet mechanisms linking intestinal microbial dysbiosis to metabolic dysfunction remain incompletely understood. Although bacterial alterations have been extensively characterised, the gut mycobiome has received comparatively limited attention despite growing evidence that fungi participate in immune, epithelial, and metabolic homeostasis. This review synthesises evidence linking gut fungal dysbiosis with T2DM from human and experimental studies. Across cohorts, T2DM has been associated with Candida enrichment and depletion of Saccharomyces, alongside glycemia-associated genera including Wickerhamomyces and Kodamaea that correlate with fasting glucose and HbA1c. Experimental studies suggest that fungal dysbiosis may contribute to epithelial barrier disruption, metabolic endotoxaemia, adipose inflammation, hepatic insulin resistance, NLRP3 inflammasome activation, β-cell dysfunction, and Th17/Treg imbalance. Cross-kingdom fungal-bacterial interactions may influence short-chain fatty acid production and bile acid signaling, while hyperglycemia may favour fungal expansion. Recent animal studies suggest that early-life mycobiome colonization may influence pancreatic β-cell development through macrophage-dependent mechanisms. Precision-mycobiome approaches suggest that baseline fungal signatures may be associated with differential metabolic responses to intervention. The available evidence remains associative, geographically concentrated, and methodologically heterogeneous. Future progress will depend on longitudinal studies, standardised profiling protocols, medication-stratified analyses, and rigorously powered clinical trials with mycobiome-specific endpoints.