Multi-omics analysis provides insights into mechanisms of intestinal fungi adaptation to dietary carbohydrates

Carbohydrates are essential energy sources in the diets of humans and animals, yet the mechanisms underlying their utilization by gut fungi remain poorly understood. To address this gap, we employed <i>Candida albicans</i>-a prevalent gut fungal species in humans and pigs-as a model to investigate fungal carbohydrate utilization strategies. Using a multi-omics approach integrating transcriptomic and metabolomic analyses, we examined fungal growth dynamics, carbohydrate degradation patterns, and enzyme activity during in vitro fermentation. Our results revealed that <i>C. albicans</i> preferentially utilizes soluble polysaccharides, such as inulin and mannan-oligosaccharides (MOS), while exhibiting lower efficiency in degrading starch. Integrated transcriptomic and metabolomic analyses identified distinct metabolites and differentially expressed genes associated with carbohydrate metabolism, with strong correlations observed between carbohydrate-active enzymes (CAZymes) and specific metabolic intermediates. Notably, CAZyme expression was substrate-dependent: inulin specifically induced glycoside hydrolase family 15 (GH15, EC 3.2.1.3), which targets α-1,2-glycosidic linkages, whereas MOS upregulated a broader set of enzymes-including GH13_40 (EC 3.2.1.10), GH15, GH16_2 (EC 3.2.1-/2.4.1-) and GH17 (EC 3.2.1.58/2.4.1-) - that act on β-1,4-, α-1,6-, α-1,2-, and α-1,3-glycosidic bonds, mediating efficient extracellular hydrolysis of complex carbohydrates into absorbable monosaccharides. This study highlights the critical role of gut fungi in dietary carbohydrate utilization and provides novel insights into the mechanisms by which CAZymes mediate fungal carbohydrate metabolism.