Cross-kingdom metabolic interactions govern Candida albicans overgrowth and colitis progression

Inflammatory bowel disease is shaped by complex microbial communities, yet the contribution of fungal-bacterial interactions to disease progression remains poorly defined. Here, we identify Cladosporium tenuissimum (C. tenuissimum) as a gut fungus with potent colitis-alleviating activity. Mechanistically, C. tenuissimum restrains Candida albicans (C. albicans) overgrowth through nutrient competition, particularly via the utilization and subsequent limitation of the amino acid ornithine. C. albicans can evade this suppression and potentiate intestinal inflammation through nutrient escape by preferentially exploiting specific amino acids, such as threonine. We further reveal a bacterial-fungal metabolic axis in which threonine-producing Bacteroides fragilis facilitates C. albicans escape from gut microbiome-mediated fungal control, thereby exacerbating colitis. Notably, dietary threonine restriction markedly attenuates C. albicans-driven colitis in mice. Together, our findings uncover a cross-kingdom metabolic network that determines C. albicans homeostasis and, in turn, governs intestinal inflammatory outcomes, offering new conceptual and therapeutic avenues for IBD.